Bullous pemphigoid IgG induces BP180 internalization via a macropinocytic pathway.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease induced by pathogenic autoantibodies against a type II transmembrane protein (BP180, collagen type XVII, or BPAG2). In animal models, BP180 autoantibody-antigen interaction appears insufficient to develop blisters, but involvement of complement and neutrophils is required. However, cultured keratinocytes treated with BP-IgG exhibit a reduction in the adhesive strength and a loss of expression of BP180, suggesting that the autoantibodies directly affect epidermal cell-extracellular matrix integrity. In this study, we explored the consequences of two distinct epithelial cells treated with BP-IgG, particularly the fate of BP180. First, we followed the distribution of green fluorescent protein-tagged BP180 in an epithelial cell line, 804G, and normal human epidermal keratinocytes after autoantibody clustering. After BP-IgG treatment, the adhesive strength of the cells to their substrate was decreased, and BP180 was internalized in both cell types, together with the early endosomal antigen-1. By using various endocytosis inhibitors and a fluid-uptake assay, we demonstrated that BP-IgG-induced BP180 internalization is mediated via a macropinocytic pathway. Moreover, a macropinocytosis inhibitor rescued a BP-IgG-induced reduction in the adhesive strength of the cells from their substrate. The results of this study suggest that BP180 internalization induced by BP-IgG plays an important role in the initiation of disease pathogenesis.

Spatial and temporal control of laminin-332 and -511 expressions during hair morphogenesis.

Hair is one of the smallest organs, but has many important functions to mammals. Hair morphogenesis occurs through the reciprocal exchange of epithelial and mesenchymal signals. There are some reports about the expression of laminin-511 and -332 during hair morphogenesis, but are no reports of the chronological expression and function of laminin-511 and its counter regulator laminin-332 during hair morphogenesis. Our results of immunoblotting revealed that laminin-332 proteins were detected at stage 0 and downregulated during stage 1 to stage 2, and then recovered at stage 3. However, laminin α5 expression was constant throughout stages 0-3. According to the results of semi-quantitative RT-PCR, the mRNA expression of all laminin-332 subunits increased gradually from stage 0 to stage 2, while the mRNA expression of all laminin-511 subunits remained constant from stage 0 to stage 3. Our results suggest that the proper expression of laminin-332 and laminin-511 may regulate appropriate hair morphogenesis.

Inducible nitric oxide synthase plays important roles in allergic reactions of pollinosis in mice sensitized with pollen allergy.

To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO-synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we analyzed changes in the frequency of sneezing, plasma levels of NO metabolites, α-melanocyte-stimulating hormone (MSH) and immunoglobulin E and tracheal expression of IgA and mast cell tryptase in control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized with Cry j I antigen. After the last intranasal challenge of antigen, changes in the frequency of sneezing and plasma levels of IgE, α-MSH and NO metabolites and tracheal expression of iNOS, IgA and mast cell tryptase were analyzed by ELISA and immunohistochemistry using specific antibodies. The sensitization of mice with Cry j I antigen increased plasma levels of NO metabolites, α-MSH and IgE and tracheal expression of iNOS, IgA and mast cell tryptase in control not but in iNOS(-/-) mice. Administration of N(G)-nitro-L-arginine methyl ester strongly inhibited all these changes occurred in control mice. These results indicate that the symptom of pollinosis including sneezing is enhanced by iNOS derived NO through activation of α-MSH-receptor containing mast cells enriched with tryptase.

Mild exercise suppresses exacerbation of dermatitis by increasing cleavage of the ß-endorphin from proopiomelanocortin in NC/Nga mice.

This study investigated the mechanism by which the strength and weakness of exercise stress affects the skin symptoms of atopic dermatitis (AD). Specific pathogen-free (SPF) and conventional NC/Nga mice were used. Conventional mice, but not the SPF, spontaneously develop dermal symptoms similar to that of patients with AD. There were two types of stress, mild (20 m/min for 60 min) or strong exercise (25 m/min for 90 min), using a treadmill four times per day. The symptom of the conventional group were strongly exacerbated by strong exercise but ameliorated by mild exercise. The plasma concentrations of α-melanocyte stimulating hormone (α-MSH) and the expression of melanocortin receptor-1 in skin elevated after strong exercise but decreased after mild exercise. The plasma levels of ß-endorphin and the expression of µ-opioid receptor in skin were increased by mild exercise. In addition, the expression of prohormone convertase (PC) 1/3, PC2 and carboxypeptidase E (CPE) in pituitary gland were higher in the conventional group than in the SPF group. The level of PC2 was suppressed by mild exercise in the conventional groups, and elevated further by strong exercise. The level of PC1/3 becomes higher with the increase of the exercise load. On the other hand, the expression of the CPE was further increase by mild exercise but suppressed by strong exercise. These observations suggested that exercise-induced stress significantly affect the symptoms of AD in a pivotal manner depending on the levels of α-MSH and ß-endorphin, and the expression of pituitary PC2 and CPE.

[A case of recurrent pancreatic cancer effectively responding to S-1 combined irinotecan third-line chemotherapy with PSK].

A case of recurrent pancreatic cancer effectively responded to S-1 and irinotecan combined with third-line chemotherapy (IRIS) with PSK. The patient was a 75-year-old female. In October 2007, a pancreatoduodenectomy was performed, followed with 6 courses of systemic adjuvant chemotherapy of gemcitabine (GEM). Three months after finishing the adjuvant chemotherapy, a recurrence of para-aortic lymph node metastasis was confirmed. We resumed the second-line chemotherapy of S-1/GEM (GS) with PSK. GS therapy was continued for about 3 years, until the recurrent lesion was found to have increased after 30 courses. Nevertheless, we continued up to 39 courses. In November 2011, we started third-line chemotherapy using S-1/irinotecan (IRIS) with PSK. The regimen was S-1 of 80 mg/body/day, continuously administered for day 1-14th, followed by a discontinuation for 2 weeks. CPT-11 100 mg/body/day was administered on day 1 and 15th; and PSK of 3 g/ body/day was continued, until it resulted in increased recurrent lesions. After the end of 4 courses, recurrent lesions started to respond partially. Currently, the patient is being treated as an outpatient. This case indicates that IRIS (S-1/CPT-11) is an effective therapy when pancreatic cancer fails to respond to GS therapy.

Intercellular pathway through hyaluronic acid in UVB-induced inflammation.

Ultraviolet B (UVB) radiation induces inflammation in the skin specifically at the site of exposure. We unexpectedly found that UVB-induced inflammation was not induced in gp91phox-depleted mice. To test whether gp91phox is directly involved in UVB-induced inflammation, neutrophil- and hyaluronic acid-depleted mice were also irradiated and examined for their response. Hyaluronic acid-depleted mice showed strongly inhibited UVB-induced inflammation, but the neutrophil-depleted mice did not exhibit any suppressed UVB-induced inflammation. To elucidate the pathway by which UVB irradiation induced inflammation, we examined the expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) and caspase-1 in the mouse skin. An increase in the expression of NLRP3 and caspase-1 was seen following the UVB irradiation of C57BL mice; however, the UVB-irradiated gp91phox-knockout (gp91phox(-/-)) mice did not have this increase in expression. Furthermore, the plasma IL-1ß level increased after the UVB irradiation in C57BL mice, but there was no change in the gp91phox(-/-) mice. These results clearly indicate that nicotinamide adenine dinucleotide phosphate oxidase is activated by gp91phox, which is expressed on the surface in response to the increased expression of hyaluronic acid induced by UVB irradiation, and as result, the generation of reactive oxygen species (ROS) increases. This ROS activate NLRP3, and NLRP3 leads to the production of caspase-1, which subsequently increases IL-1ß, thereby finally inducing inflammation. It is thought that this system may play an important role in the damage and ageing of skin, and further studies are necessary to confirm these finding.

Lipoma with bone and cartilage components in the left axilla of a middle-aged woman.

UNLABELLED: Lipoma is the most common type of benign soft tissue tumor. However, lipoma containing bone or cartilage is very rare, especially a tumor containing both of these components. We encountered a 59-year-old woman who had a benign lipoma of the infraspinatus muscle that contained both osseous and chondral components. Histopathological examination revealed the presence of chondral and osseous elements mixed with mature adipose tissue. To the best of our knowledge, there has never been a report of benign lipoma containing osteochondral tissue at this location. Therefore, we report the first case of an axillary lipoma with bone and cartilage components. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article.

A technique for auricular keloid core excision using a skin biopsy punch.

BACKGROUND: Keloids of the auricular region, resulting from ear piercing or external injury, are a common cosmetic problem. Surgical treatment followed by conservative management often is needed. The "hollowing out method for keloids of the auricle" retains the skin over the keloid lesion to minimize tension on the wound. This is considered to be the appropriate surgical treatment method, but skill is required to remove the keloid and retain the skin with a uniform thickness and appropriate form. MATERIAL AND METHODS: Four patients with auricle keloids were included in this study. All the patients were females between the ages of 18 and 29 years (average age, 24.8 years). Keloid core excision using a skin biopsy punch with the patient under local anesthesia was performed for all the patients. RESULTS: Use of a skin biopsy punch resulted in a shorter operating time without causing ear deformity. CONCLUSION: The authors report a technique for keloid core excision using a skin biopsy punch and believe it is a useful method LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Intense pulsed light therapy for aberrant Mongolian spots.

BACKGROUND: Aberrant Mongolian spots (AMS) distal to the lumbosacral region are thought to be more likely to persist than typical sacral Mongolian spots. So far, Q-switched ruby laser (QSRL) has been the treatment of choice for AMS. Intense pulsed light (IPL) is obtained from flashlamp devices that emit wavelengths between 515 and 1200 nm. IPL has documented efficacy for the treatment of irregular pigmentation, telangiectasia, rough skin texture, rhytids, hair removal, and vascular lesions, with several filters being available that can be used to block shorter wavelengths from the skin. As far as we could determine, there have been no clinical and histological studies on the treatment of AMS with IPL. Accordingly, the aim of this study was to assess the clinical and histological efficacy of IPL for AMS. METHODS: Seven patients (4 males and 3 females) presenting from September 2008 to July 2009 were assessed. Their mean age was 2.0 years, ranging from 0 to 7 years. The IPL device used in this study was a Natulight (Lumenis Ltd., Tokyo, Japan). Photographs were taken of all patients with a high-resolution digital camera at baseline and 6 months after treatment. Skin biopsy specimens were taken from 1 patient (case 4) before, immediately after, and 6 months after treatment. RESULTS: According to the 7 family members of the patients, the outcome of IPL was graded as follows: excellent improvement in 1 (14%), good improvement in 4 (57%), and slight improvement in 2 (29%). All families would have liked to continue IPL treatment. Evaluation of the effect of treatment by a physician was less favorable, with excellent improvement in 1 (14%), good improvement in 2 (29%), and slight improvement in 4 (57%). Histopathologic examination of the pigmented region revealed the typical features of a Mongolian spot in the hematoxylin-eosin stained section. Immediately after IPL, there were no changes in the dermis. At 6 months after treatment, however, the number of melanocytes in the middle and upper dermis was obviously decreased. CONCLUSIONS: IPL is an effective method for the treatment of AMS.

Dye laser photodynamic therapy for Bowen's disease in a patient with epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare heritable skin disease that results in unusual susceptibility to infection with specific types of human papillomavirus (HPV). Here we report a 53-year-old man with EV who developed Bowen's disease on his lower eyelid and the chest. Mutation analysis of EVER1 gene revealed homozygous splice acceptor site mutation (IVS8-2, A > T). In this patient, HPV3, HPV14, and HPV38 had been identified from the skin lesions. The Bowen's skin lesion on the left lower eye-lid was treated by photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) and pulsed dye laser (PDL). After two rounds of the PDT treatment, the skin lesion disappeared and a skin biopsy confirmed the efficacy of the treatment. This method was simple, less invasive than other treatments, and achieved a satisfactory cosmetic result.

Two cases of steatocystoma simplex in infants.

Steatocystoma simplex is a rare benign cutaneous cyst that is thought to be a circumscribed malformation arising from the pilosebaceous duct junction. Reports describing steatocystoma simplex are scarce and many issues remain to be clarified, including frequency and age distribution. Steatocystoma simplex is generally considered to be a solitary, non-inherited tumor arising in adults; there have been no previous reports of steatocystoma simplex in infants. We encountered two cases of steatocystoma simplex arising on the head in infants less than 2 years old. Herein we discuss the clinical and pathological characteristics of these cases.

Inducible nitric oxide synthase (iNOS) and α-melanocyte-stimulating hormones of iNOS origin play important roles in the allergic reactions of atopic dermatitis in mice.

To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analysed the differences in ear thickness, the frequency of scratching and plasma levels of ovalbumin-specific immunoglobulin E (OVA-IgE), transforming growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, adrenocorticotropic hormone (ACTH) and α-melanocyte-stimulating hormone (α-MSH) between control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized three times with OVA antigen. Before and after the last skin sensitization, the number of scratching incidents and the thickness of the ear were examined, and the plasma levels of OVA-IgE, α-MSH, ACTH, TGF-ß and TNF-α were analysed by ELISA. Sensitization of mice with OVA resulted in increased plasma levels of OVA-IgE, α-MSH, ACTH, TGF-ß and TNF-α in control, but not in iNOS(-/-) mice. The administration of l-nitro-arginine-methyl ester (l-NAME) abolished all the above changes that occurred in the control mice. In addition, iNOS(-/-) mice given α-MSH exhibited a change similar to that seen in the control, whereas iNOS(-/-) mice given ACTH, TGF-ß or TNF-α did not demonstrate any changes. These results indicate that symptoms of AD such as scratching can be exacerbated by α-MSH, which is induced by iNOS-derived NO.

Unilateral eyelid angioedema with congestion of the right bulbar conjunctiva due to loxoprofen sodium.

Angioedema is a variant of urticaria that causes deep dermal and subcutaneous swelling. It frequently is a unilateral reaction and usually lasts for several hours but may persist for several days. We report 2 cases of angioedema that involved the right upper and lower eyelids and was associated with congestion of the right bulbar conjunctiva; the symptoms started approximately 1 to 2 hours after taking loxoprofen sodium. All of the symptoms subsided after oral corticosteroid therapy. In both cases, an oral challenge test with 60 mg of loxoprofen sodium (contained in a tablet) caused swelling of the right upper eyelid within several hours, followed by swelling of the right bulbar conjunctiva. We believe the drug reaction in both patients is angioedema.

Histological differentiation, histogenesis and prognosis of cutaneous angiosarcoma.

BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare, extremely malignant vascular tumor. The optimum treatment for patients with CAS has not been defined because of its exremely rarity. As prognostic factors in patients with CAS, tumor less than 5 cm in size has a better prognosis. Although tumor differentiation in other sarcoma is an important prognostic factor, tumor differentiation in CAS is not a prognostic factor. CAS is thought as a collection of hemangiosarcoma, lymphangiosarcoma, tumors which cannot be classified as of vascular and lymphatic origin, or mixed tumor of both. Histogenesis of CAS have not been clarified yet. We tried to classify histogenesis by immunohistochemistry and evaluate the prognosis among histogeneses. METHODS: Using immunohistochemistry, we classified histogenesis of CAS in 20 patients who visited Osaka City University Hospital between 1998 and 2008. RESULTS: From the results of immunohistochemical staining with CD34 and D2-40, histogenesis of CAS can be divided into vascular type (CD34 positive D2-40 negative), mixed type (CD34 positive D2-40 positive), and lymphatic type (CD34 negative D2-40 positive). Vascular type was found in 2 cases, mixed type in 5 cases, and lymphatic type in 13 cases. Survival rates were not significantly affected by histogenesis, however, survival rate of mixed type was better than those of others. CONCLUSIONS: CAS can be divided into vascular type, mixed type, and lymphatic type based on immunohistochemistry. Because of a small group, we did not suggest that histogenesis of CAS was related with prognosis. We speculate that antiangiogenic agents might be important in the treatment based on histogeneses in CAS. In the future, further accumulation of chemotherapeutic cases might upgrade histogenesis classification as an important prognostic factor in the treatment of CAS.

Bilateral nevus of Ota: a rare manifestation congenital type in a boy.

BACKGROUND: The nevus of Ota is usually characterized by small, flat, unilateral, blue-black or gray-brown spots occurring on skin innervated by the first or second branch of the trigeminal nerve. It comprises dermal melanocytes, presumably arising due to the dermal arrest of cells migrating from the neural crest. Nevus of Ota is 3-5 times more common in women than men, and is classified into congenital type, appearing soon after birth, and acquired type, appearing during or after puberty. METHODS: We report on a six-year-old Japanese boy with the bilateral nevus of Ota. He was referred to our hospital because of bilateral hyperpigmentation of the face, present since birth. Our treatment consisted of Q-switched ruby laser irradiation under general anesthesia. The Q-switched ruby laser (Model IB101; Niic Co. Ltd., Tokyo, Japan), had a wavelength of 694.3 nm, a spot size of 5 mm, a 1 Hz repetition rate, a pulse duration of 20 nsec and fluence ranged from 3.0 J/cm2 to 6.0 J/cm2. RESULTS: Q-switched ruby laser irradiation improved his pigmentation, and will therefore be repeated several times. CONCLUSIONS: This case of congenital bilateral nevus of Ota in a young male patient was very rare. And Q-switched ruby laser irradiation was effective as same as another nevus of Ota.

Increased alpha-melanocyte-stimulating hormone (alpha-MSH) levels and melanocortin receptors expression associated with pigmentation in an NC/Nga mouse model of atopic dermatitis.

Patients with a specific subtype of atopic dermatitis (AD) display particular patterns of pigmentation, such as ripple pattern pigmentation on the neck, pigmented macules on the lip and diffuse pigmentation. However, the mechanism underlying these patterns has not been determined. The purpose of our research is to investigate the factors influencing this type of pigmentation in AD. We observed that AD model mice (NC/Nga mice) displayed an increase in the number of 3, 4-dihydroxyphenylalanine (Dopa)-positive melanocytes in the epidermis and intestine (jejunum and colon) while in the inflammatory state. The plasma levels of alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocoticotropin (ACTH) also increased in NC/Nga mice with dermatitis. Furthermore, the expression of melanocortin receptor 5 and melanocortin receptor 1 (MC1R) increased in the skin, and melanocortin receptor 3 (MC3R) expression increased in the intestine. However, the changes in the Dopa-positive cells of conventional NC/Nga mice were not induced by treatment with either agouti (an MC1R antagonist) or agouti-related protein (an MC3R antagonist). These results indicate that the pigmentation of AD is related to increased levels of alpha-MSH, MC1R (in the skin) and MC3R (in the intestines).

Strong exercise stress exacerbates dermatitis in atopic model mice, NC/Nga mice, while proper exercise reduces it.

Atopic dermatitis is well known to exacerbate by stress. How the influence of exercise stress on the skin symptoms in patients with atopic dermatitis has not been clarified. The purpose of our research is to investigate how different strength of exercise stress acts on atopic dermatitis. Specific pathogen-free (SPF) and conventional NC/Nga male mice were used for the experiments. Conventional mice but not SPF group spontaneously develop dermal symptom similar to that of patients with atopic dermatitis at their age of 7 weeks. They were given two types of stress, mild (20 m/min for 60 min) or strong exercise (25 m/min for 90 min), using a treadmill four times per day. The dermal symptom of the conventional group was strongly exacerbated by strong exercise but ameliorated by mild exercise. Under the standard experimental conditions, plasma concentrations of α-melanocyte-stimulating hormone (α-MSH), transforming growth factor-ß (TGF-ß) and substance P in conventional mice increased markedly with concomitant exacerbation of the symptom. The plasma concentrations of these proteins elevated after strong exercise but decreased after mild exercise. Under the conventional conditions, plasma levels of ß-endorphin increased with time by some mechanisms enhanced by the mild exercise. These observations suggested that exercise-induced stress significantly affect the symptom of atopic dermatitis in a pivotal manner depending on the plasma levels of TGF-ß, α-MSH, substance P and ß-endorphin.

Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo (Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study.

Hochu-ekki-to is a traditional herbal (Kampo) medicine that has been shown to be effective for patients with Kikyo (delicate, easily fatigable, or hypersensitive) constitution. Previous case reports have suggested that this herbal drug was effective for a certain subgroup of patients with atopic dermatitis (AD). We aimed to evaluate the efficacy and safety of Hochu-ekki-to in the long-term management of Kikyo patients with AD. In this multicenter, double blind, randomized, placebo-controlled study, 91 Kikyo patients with AD were enrolled. Kikyo condition was evaluated by a questionnaire scoring system. All patients continued their ordinary treatments (topical steroids, topical tacrolimus, emollients or oral antihistamines) before and after their protocol entry. Hochu-ekki-to or placebo was orally administered twice daily for 24 weeks. The skin severity scores, total equivalent amount (TEA) of topical agents used for AD treatment, prominent efficacy (cases with skin severity score = 0 at the end of the study) rate and aggravated rate (more than 50% increase of TEA of topical agents from the beginning of the study) were monitored and evaluated. Seventy-seven out of 91 enrolled patients completed the 24-week treatment course (Hochu-ekki-to: n = 37, placebo: n = 40). The TEA of topical agents (steroids and/or tacrolimus) was significantly (P < 0.05) lower in the Hochu-ekki-to group than in the placebo group, although the overall skin severity scores were not statistically different. The prominent efficacy rate was 19% (7 of 37) in the Hochu-ekki-to group and 5% (2 of 40) in the placebo group (P = 0.06). The aggravated rate was significantly (P < 0.05) lower in the Hochu-ekki-to group (3%; 1 of 37) than in the placebo group (18%; 7 of 39). Only mild adverse events such as nausea and diarrhea were noted in both groups without statistical difference. This placebo-controlled study demonstrates that Hochu-ekki-to is a useful adjunct to conventional treatments for AD patients with Kikyo constitution. Use of Hochu-ekki-to significantly reduces the dose of topical steroids and/or tacrolimus used for AD treatment without aggravating AD.

Comparison of regional efficacy and complications in the treatment of aberrant Mongolian spots with the Q-switched ruby laser.

BACKGROUND AND OBJECTIVE: Aberrant Mongolian spots (AMS) distal from the lumbosacral region are said to be more apt to persist than the typical sacral AMS, so the Q-switched ruby laser (QSRL) has been the treatment of choice for AMS. However, so far as we could determine, there is no statistical analysis of the treatment of AMS. This paper shows statistical comparisons of the efficacy and complications in the treatment of AMS with QSRL. METHODS: Fifty-three patients (16 males and 37 females) with 57 AMS regions were treated with the QSRL from March 1999 to April 2007, and we divided the diseased areas into exposed regions that could not be concealed by clothing and non-exposed regions that could be concealed by clothing, and performed a statistical analysis. RESULTS: The results indicated that QSRL treatment of AMS in the exposed regions showed significantly improved coloration and caused less pigmentation when compared with the non-exposed regions. CONCLUSION: We concluded that QSRL treatment of AMS in the exposed regions is more effective than that of AMS in the non-exposed regions.

Enhancement of anti-allergic effects mediated by the Kampo medicine Shoseiryuto (Xiao-Qing-Long-Tang in Chinese) with lysed Enterococcus faecalis FK-23 in mice.

Kampo is a traditional Japanese medicine originating from ancient Chinese medicine which included the administration of herbal prescription, lifestyle advice and acupuncture. Orally administered Kampo prescriptions are believed to be influenced by diet and intestinal microbiota. However, reports on the Kampo administration effects are still limited. Shoseiryuto (TJ-19), which has anti-allergic and anti-inflammatory properties, is a Kampo prescription used clinically for the treatment of allergic bronchial asthma. We examined whether Shoseiryuto administration is affected by a probiotic product, lysed Enterococcus faecalis FK-23 (LFK). BALB/c mice were sensitized with cedar pollen allergen, and the peritoneal accumulation of eosinophils was induced. During a sensitization period of 21 days, varying amounts of Shoseiryuto (and saline as a control) were administered to the mice. The accumulation of eosinophils was significantly reduced by 30 mg/day doses of Shoseiryuto but not by 3 or 9 mg/day doses. Similarly, 3 mg/day Shoseiryuto, 30 mg/day LFK, 3 mg/day of Shoseiryuto co-administered with 30 mg/day of LFK, and saline control were compared. A significant reduction in the accumulation of eosinophils was observed at 3 mg/day Shoseiryuto co-administered with 30 mg/day of LFK. These results suggest that Shoseiryuto-mediated anti-allergic effects are enhanced by the probiotic (LFK). Although not significant statistically, serum allergen-specific and total IgE levels in the treatment group exposed to the mixed agent (ie. Shoseiryuto and LFK) were generally lower than those receiving either one alone. The results indicate a synergistic effect of a Kampo medicine (Shoseiryuto, Xiao-Qing-Long-Tang in Chinese) and lysed Enterococcus faecalis FK-23 on allergic responses in mice.