Desmin interacts with STIM1 and coordinates Ca2+ signaling in skeletal muscle.

Stromal interaction molecule 1 (STIM1), the sarcoplasmic reticulum (SR) transmembrane protein, activates store-operated Ca2+ entry (SOCE) in skeletal muscle and, thereby, coordinates Ca2+ homeostasis, Ca2+-dependent gene expression, and contractility. STIM1 occupies space in the junctional SR membrane of the triads and the longitudinal SR at the Z-line. How STIM1 is organized and is retained in these specific subdomains of the SR is unclear. Here, we identified desmin, the major type III intermediate filament protein in muscle, as a binding partner for STIM1 based on a yeast 2-hybrid screen. Validation of the desmin-STIM1 interaction by immunoprecipitation and immunolocalization confirmed that the CC1-SOAR domains of STIM1 interact with desmin to enhance STIM1 oligomerization yet limit SOCE. Based on our studies of desmin-KO mice, we developed a model wherein desmin connected STIM1 at the Z-line in order to regulate the efficiency of Ca2+ refilling of the SR. Taken together, these studies showed that desmin-STIM1 assembles a cytoskeletal-SR connection that is important for Ca2+ signaling in skeletal muscle.

Increased expression of desmin and vimentin reduces bladder smooth muscle contractility via JNK2.

Bladder dysfunction is associated with the overexpression of the intermediate filament (IF) proteins desmin and vimentin in obstructed bladder smooth muscle (BSM). However, the mechanisms by which these proteins contribute to BSM dysfunction are not known. Previous studies have shown that desmin and vimentin directly participate in signal transduction. In this study, we hypothesized that BSM dysfunction associated with overexpression of desmin or vimentin is mediated via c-Jun N-terminal kinase (JNK). We employed a model of murine BSM tissue in which increased expression of desmin or vimentin was induced by adenoviral transduction to examine the sufficiency of increased IF protein expression to reduce BSM contraction. Murine BSM strips overexpressing desmin or vimentin generated less force in response to KCl and carbachol relative to the levels in control murine BSM strips, an effect associated with increased JNK2 phosphorylation and reduced myosin light chain (MLC20 ) phosphorylation. Furthermore, desmin and vimentin overexpressions did not alter BSM contractility and MLC20 phosphorylation in strips isolated from JNK2 knockout mice. Pharmacological JNK2 inhibition produced results qualitatively similar to those caused by JNK2 knockout. These findings suggest that inhibition of JNK2 may improve diminished BSM contractility associated with obstructive bladder disease.

Giant Cell Poor Extra-Articular Diffuse-Type Tenosynovial Giant Cell Tumor With Extensive Desmin Expression: A Potential Diagnostic Pitfall With Cytogenetic Confirmation.

Diffuse-type tenosynovial giant cell tumor can rarely present as an entirely extra-articular mass, which can be misdiagnosed as a sarcoma especially when giant cells are absent, dominated by large dendritic mononuclear cells, and desmin expression is extensive.

Interleukin-17A participates in podocyte injury by inducing IL-1ß secretion through ROS-NLRP3 inflammasome-caspase-1 pathway.

Studies show that the Th17/IL-17A axis plays an important role in the pathogenesis of kidney diseases. Previously, we also showed that IL-17A may play a role in the pathogenesis of primary nephrotic syndrome; however, the underlying mechanism(s) is unclear. The aim of this study was to explore the molecular mechanism of IL-17A-inducing podocyte injury in vitro. In this study, the NLRP3 inflammasome activation and the morphology of podocytes were detected by Western blot and immunofluorescence. The results showed that podocytes persistently expressed IL-17A receptor and that NLRP3 inflammasome in these cells was activated upon exposure to IL-17A. Also, activity of caspase-1 and secretion of IL-1ß increased in the presence of IL-17A. In addition, IL-17A disrupted podocyte morphology by decreasing expression of podocin and increasing expression of desmin. Blockade of intracellular ROS or inhibition of caspase-1 prevented activation of the NLRP3 inflammasome, thereby restoring podocyte morphology. Taken together, the results suggest that IL-17A induces podocyte injury by activating the NLRP3 inflammasome and IL-1ß secretion and contributes to disruption of the kidney's filtration system.

Compared With Elastin Stains, h-Caldesmon and Desmin Offer Superior Detection of Vessel Invasion in Gastric, Pancreatic, and Colorectal Adenocarcinomas.

BACKGROUND: The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens. MATERIALS AND METHODS: We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used. RESULTS: There were 369 foci. The smooth muscle markers were more sensitive than the elastin stains, and h-caldesmon more sensitive than desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by desmin and h-caldesmon, whereas the elastin stains were not ( P = .001). h-Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin stains were negative ( P = .000). In 16 (20.5%) foci, h-caldesmon was the only positive marker ( P = .002). Among 152 type X foci, 91 (59.9%) were positive by all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the 2 elastin stains ( P = .001). CONCLUSION: We recommend these stains for suspect foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might highlight both predictable and unpredictable foci.

The role of intermediate filaments in maintaining integrity and function of intestinal epithelial cells after massive bowel resection in a rat.

PURPOSE: Intermediate filaments (IFs) are a part of the cytoskeleton that extend throughout the cytoplasm of all cells and function in the maintenance of cell-shape by bearing tension and serving as structural components of the nuclear lamina. In normal intestine, IFs provide a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. The purpose of this study was to evaluate the role of IFs during intestinal adaptation in a rat model of short bowel syndrome (SBS). MATERIALS AND METHODS: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75% bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression (DGE) analysis was used to determine the cytoskeleton-related gene expression profiling. IF-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry. RESULTS: Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 16 cytoskeleton-related genes were investigated. Between these genes, only myosin and tubulin levels were upregulated in SBS compared to sham animals. Between IF-related genes, desmin, vimentin and lamin levels were down-regulated and keratin and neurofilament remain unchanged. The levels of TGF-ß, vimentin and desmin gene and protein were down-regulated in resected rats (vs sham animals). CONCLUSIONS: Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by a stimulated microfilaments and microtubules, and by inhibited intermediate filaments. Resistance to cell compression rather that maintenance of cell-shape by bearing tension are responsible for contraction, motility and postmitotic cell separation in a late stage of intestinal adaptation.

Drug use to resistance exercise-induced fatigue based on diclofenac diethylamine emulgel efficacy analysis.

In this paper, the author study on the effect of drug treatment on sports injury, and makes a comparative analysis of drug effects. In sports, the incidence of various types of injuries is increasing, especially in muscle injury. In the experiment, we compared the effects of three different drugs on the treatment and relief of muscle loss. After 3 weeks, the average optical density of desmin in muscle fiber positive region have decreased, as xiaotong plaster (0.4708±0.0126), votalin (0.5124±0.0264) and placebo (0.3856±0.0312). It has a certain effect to promote the repair and regeneration of desmin expression by drugs. Through the analysis of the effect of drug intervention on sports injury repair, we can effectively improve the therapeutic effect of sports injury.

Pseudosarcomatous Vaginal Polyp.

BACKGROUND: Although rare, pregnant women can present with fibroepithelial polyps of the vagina. Most likely hormonally related, these polyps have been described in various locations of the lower female genital tract. They can be mistaken for malignant lesions due to hypercellularity and cytologic atypia. CASE: We describe the case of a 31-year-old woman who presented with a polyp of the vagina during a postpartum visit. RESULTS: Atypical cells were seen in hypercellular areas of the stroma of the polyp. CONCLUSION: A pitfall to avoid is classifying these benign lesions as malignant based on atypical histopathology.

Osteogenic Melanoma With Desmin Expression.

BACKGROUND: Osteogenic differentiation is rarely seen in melanomas, when it occurs it is mainly in acral lesions. METHODS: We report a case of an osteogenic melanoma in a 49-year-old woman who presented with a pigmented lesion in the subungueal region of her left hallux. The lesion was ulcerated and infiltrated until the deep dermis without bone involvement. RESULTS: The tumor was composed of pleomorphic atypical epithelioid and fusiform cells disposed in nests or cords, with vesicular nuclei and prominent central nucleoli. Focal lentiginous proliferation of large atypical melanocytes was present along the dermoepidermal junction. Areas of osteoid matrix focally mineralized were disposed in trabeculae, and there were islands of neoplastic cells. Immunohistochemistry revealed strong expression of S-100 protein and, unexpectedly, of desmin. Focal expression of Melan-A, microphthalmia transcription factor, and HMB-45 is also revealed. Mutations in BRAF and NRAS genes were not present. The patient was submitted to an amputation of the left hallux with negative sentinel lymph node. CONCLUSION: The importance of recognizing osteogenic melanoma is based on difficulties for histologic recognition and its differentials diagnosis.

Histopathological and Immunohistochemical Evaluation of Pannus Tissue in Patients with Prosthetic Valve Dysfunction.

BACKGROUND: Prosthetic valve dysfunction due to pannus formation is a rare but serious complication. Currently, limited data are available concerning the pathogenesis and immunohistochemical properties of pannus. The study aim was to investigate the morphological, histopathological and immunohistochemical characteristics of pannus formation in patients with prosthetic valve dysfunction. METHODS: A total of 35 patients (10 males, 25 females; mean age 44 ± 16 years) who had undergone re-do valve surgery due to prosthetic valve obstruction was enrolled in the study. Immunohistochemical studies were aimed at evaluating the expression of alphasmooth muscle actin (α-SMA) and desmin in myofibroblasts and smooth muscle cells; epithelial membrane antigen (EMA) in epithelial cells; and CD34, Factor VIII and vascular endothelial growth factor (VEGF) in endothelial cells. Matrix metalloproteinases (MMPs) -2 and -9, and transforming growth factor-beta (TGF-ß) were used to demonstrate cytokine release from macrophages, leukocytes, fibroblasts and myofibroblasts. RESULTS: Pannus appeared as a tough and thick tissue hyperplasia which began from outside the suture ring in the periannular region and extended to the inflow and outflow surfaces of the prosthetic valves. Histopathological analysis showed the pannus tissue to consist of chronic inflammatory cells (lymphocytes, plasma cells, macrophages and foreign body giant cells), spindle cells such as myofibroblasts, capillary blood vessels and endothelial cells laying down the lumens. Calcification was present in the pannus tissue of 19 explanted prostheses. Immunohistochemical studies revealed positive α-SMA expression in all patients, whereas 60.5% of patients were positive for desmin, 50% for EMA, 42.1% for VEGF, 39.5% for TBF-ß, 42.1% for MMP-2, 86.8% for CD34, and 97.4% for Factor VIII. MMP-9 was negative in all patients. CONCLUSIONS: Pannus tissue appears to be formed as the result of a neointimal response in periannular regions of prosthetic valves that consist of periannular tissue migration, myofibroblast and extracellular matrix proliferation with vascular components. It is a chronic active process in which mediators such as TGF-ß, VEGF and MMP-2 play roles in both matrix formation and degradation.

[EFFECT OF SHORT-TERM DRY IMMERSION ON PROTEOLYTIC SIGNALING IN HUMAN SOLEUS MUSCLE].

The signaling processes initiating proteolytic events in m. soleus of humans during short-term exposure in the non-weight bearing conditions were analyzed. Dry immersion (DI) was used to induce weight deprivation over 3 days. Western blotting was used to define the IRS-1 content, total and phosphorylated neuronal NO-synthase (nNOS), AMP-activated protein kinase (AMPK) that control the anabolic and catabolic pathways, and concentrations of cytoskeletal protein desmin and Ca²âº-activated protease calpin. Already on day-3 of DI calpain-dependent proteolysis manifests itself by reductions in both the total content and level of nNOS phosphorilation. Moreover, AMPK phosphorilation was decreased drastically.

Umbilical cord mesenchymal stem cell-conditioned media prevent muscle atrophy by suppressing muscle atrophy-related proteins and ROS generation.

The therapeutic potential of mesenchymal stem cell-conditioned medium (MSC-CM) has been reported with various types of disease models. Here, we examine the therapeutic effect of umbilical cord MSC-CM (UCMSC-CM) on muscle-related disease, using a dexamethasone (Dex)-induced muscle atrophy in vitro model. The expressions of muscle atrophy-related proteins (MuRF-1 and MAFbx) and muscle-specific proteins (desmin and myogenin) were evaluated by Western blot analysis. The level of production of reactive oxygen species (ROS) was determined using a 2',7'-dichlorofluorescein diacetate (DCFDA) dye assay. The expression of antioxidant enzymes (copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPx-1), and catalase (CAT)) was verified by reverse transcription polymerase chain reaction (RT-PCR). When L6 cells were exposed to Dex, the expression of muscle atrophy-related proteins was increased by 50-70%, and the expression of muscle-specific proteins was in turn decreased by 23-40%. Conversely, when the L6 cells were co-treated with UCMSC-CM and Dex, the expression of muscle atrophy-related proteins was reduced in a UCMSC-CM dose-dependent manner and the expression of muscle-specific proteins was restored to near-normal levels. Moreover, ROS generation was effectively suppressed and the expression of antioxidant enzymes was recovered to a normal degree. These data imply that UCMSC-CM clearly has the potential to prevent muscle atrophy. Thus, our present study offers fundamental data on the potential treatment of muscle-related disease using UCMSC-CM.

BMP4 inhibits myogenic differentiation of bone marrow-derived mesenchymal stromal cells in mdx mice.

BACKGROUND AIMS: Bone marrow-derived mesenchymal stromal cells (BMSCs) are a promising therapeutic option for treating Duchenne muscular dystrophy (DMD). Myogenic differentiation occurs in the skeletal muscle of the mdx mouse (a mouse model of DMD) after BMSC transplantation. The transcription factor bone morphogenic protein 4 (BMP4) plays a crucial role in growth regulation, differentiation and survival of many cell types, including BMSCs. We treated BMSCs with BMP4 or the BMP antagonist noggin to examine the effects of BMP signaling on the myogenic potential of BMSCs in mdx mice. METHODS: We added BMP4 or noggin to cultured BMSCs under myogenic differentiation conditions. We then injected BMP4- or noggin-treated BMSCs into the muscles of mdx mice to determine their myogenic potential. RESULTS: We found that the expression levels of desmin and myosin heavy chain decreased after treating BMSCs with BMP4, whereas the expression levels of phosphorylated Smad, a downstream target of BMP4, were higher in these BMSCs than in the controls. Mdx mouse muscles injected with BMSCs pretreated with BMP4 showed decreased dystrophin expression and increased phosphorylated Smad levels compared with muscles injected with non-treated BMSCs. The opposite effects were seen after pretreatment with noggin, as expected. CONCLUSIONS: Our results identified BMP/Smad signaling as an essential negative regulator of promyogenic BMSC activity; inhibition of this pathway improved the efficiency of BMSC myogenic differentiation, which suggests that this pathway might serve as a target to regulate BMSC function for better myogenic differentiation during treatment of DMD and degenerative skeletal muscle diseases.

The Expression and Significance of NLRP3 Inflammasome in Patients with Primary Glomerular Diseases.

BACKGROUND/AIMS: Primary glomerulonephritis (PGN) is the most common reason inducing end stage renal disease in China, however, its pathogenesis remains unclear. The present study was designed to test the hypothesis that the formation and activation of NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasomes is an important initiating mechanism resulting in PGN. METHODS: Serum samples and frozen sections were collected from 38 cases with PGN, and renal tissues were obtained from 22 of them. NLRP3 inflammasomes were detected by RT-PCR and immunofluoresence methods. The relationship between NLRP3 and clinical/pathologic indexes was analyzed. RESULTS: RT-PCR analyses demonstrated that the mRNA levels of NLRP3 and caspase-1 genes were elevated significantly in renal tissues of PGN patients compared to those from normal pericarcinoma tissues. Moreover, the increased level of NLRP3 mRNA was correlative with a decrease in nephrin mRNA level and an increase in desmin mRNA level, which indicates that NLRP3 participates in podocyte injury in PGN patients. Immunofluorescence analysis also showed the protein expressions of NLRP3 and caspase-1 were increased in the glomeruli of PGN patients. Neverthless, there was no obvious regularity was presented in further subgroup analysis according to pathological types. In addition, increased NLRP3 was associated with the deterioration of renal function and glomerulosclerosis. IL-1ß, a product of NLRP3 inflammasome activation, had a significant correlation with proteinuria. CONCLUSIONS: The formation and activation of NLRP3 inflammasomes in podocytes has been importantly implicated in the development of PGN-associated glomerular injury.

Improved neurological outcome by intramuscular injection of human amniotic fluid derived stem cells in a muscle denervation model.

PURPOSE: The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS) have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model. MATERIALS AND METHODS: Seventy two Sprague-Dawley rats weighing 200-250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups. RESULTS: NT-3 (Neurotrophin 3), BDNF (Brain derived neurotrophic factor), CNTF (Ciliary neurotrophic factor), and GDNF (Glia cell line derived neurotrophic factor) were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index) and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology. CONCLUSION: Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection furthermore improves the nerve regeneration in a long term nerve anastomosis model.

Isolation of myofibroblasts from mouse and human esophagus.

Murine and human esophageal myofibroblasts are generated via enzymatic digestion. Neonate (8-12 day old) murine esophagus is harvested, minced, washed, and subjected to enzymatic digestion with collagenase and dispase for 25 min. Human esophageal resection specimens are stripped of muscularis propria and adventitia and the remaining mucosa is minced, and subjected to enzymatic digestion with collagenase and dispase for up to 6 hr. Cultured cells express α-SMA and vimentin and express desmin weakly or not at all. Culture conditions are not conducive to growth of epithelial, hematopoietic, or endothelial cells. Culture purity is further confirmed by flow cytometric evaluation of cell surface marker expression of potential contaminating hematopoietic and endothelial cells. The described technique is straightforward and results in consistent generation of non-hematopoieitc, non-endothelial stromal cells. Limitations of this technique are inherent to the use of primary cultures in molecular biology studies, i.e., the unavoidable variability encountered among cultures established across different mice or humans. Primary cultures however are a more representative reflection of the in vivo state compared to cell lines. These methods also provide investigators the ability to isolate and culture stromal cells from different clinical and experimental conditions, allowing comparisons between groups. Characterized esophageal stromal cells can also be used in functional studies investigating epithelial-stromal interactions in esophageal disorders.

Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I.

Pancreatic stellate cells (PSCs) play a key role in the dense desmoplastic stroma associated with pancreatic ductal adenocarcinoma. Studies on human PSCs have been minimal due to difficulty in maintaining primary PSC in culture. We have generated the first conditionally immortalized human non-tumor (NPSC) and tumor-derived (TPSC) pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase (hTERT). These cells proliferate at 33°C. After transfer to 37°C, the SV40LT is switched off and the cells regain their primary PSC phenotype and growth characteristics. NPSC contained cytoplasmic vitamin A-storing lipid droplets, while both NPSC and TPSC expressed the characteristic markers αSMA, vimentin, desmin and GFAP. Proteome array analysis revealed that of the 55 evaluated proteins, 27 (49%) were upregulated ≥3-fold in TPSC compared to NPSC, including uPA, pentraxin-3, endoglin and endothelin-1. Two insulin-like growth factor binding proteins (IGFBPs) were inversely expressed. Although discordant IGFBP-2 and IGFBP-3 levels, IGF-I was found to stimulate proliferation of both NPSC and TPSC. Both basal and IGF-I stimulated motility was significantly enhanced in TPSC compared to NPSC. In conclusion, these cells provide a unique resource that will facilitate further study of the active stroma compartment associated with pancreatic cancer.

Primary sinonasal mucosal melanoma with aberrant diffuse and strong desmin reactivity: a potential diagnostic pitfall!

The broad morphologic spectrum, inherent immunophenotypic heterogeneity of malignant melanoma and its rarity in the sinonasal tract are major challenges in eliciting the correct diagnosis, which may lead to misclassification and inadequate medical management. Herein, we describe a single case of a 70 year-old male with sinonasal mucosal melanoma, exhibiting varying histologic phenotypes including small round blue cell morphology, epithelioid and focal rhabdoid morphology and strong, diffuse desmin immunoreactivity. These constellation of features initially prompted the diagnosis of rhabdomyosarcoma. The differential diagnosis in this anatomic area includes other malignant small round blue cell tumors of the sinonasal mucosa such as rhabdomyosarcoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, and lymphoma. We reviewed precedent literature and further discuss the potential pitfalls to which pathologists may be prone.

MicroRNA-155 deficiency promotes nephrin acetylation and attenuates renal damage in hyperglycemia-induced nephropathy.

MiR-155 has been reported to be involved in both innate and adaptive immune responses. But the role of miR-155 in hyperglycemia-induced nephropathy is still unknown. In our current study, 3-month-old male wild-type C57 mice and Mir-155(-/-) mice were used to establish hyperglycemia-induced nephropathy. In our hyperglycemia-induced nephropathy model, the expression of podocyte injury marker desmin was markedly increased in the diabetes group when compared with control. Diabetes also significantly decreased the levels of nephrin and acetylated nephrin, whereas the expression of miR-155 was markedly increased in diabetes group when compared with control. MiR-155(-/-) mice showed significantly increased expression of nephrin, acetylated nephrin, and Wilm's tumor-1 protein (WT-1) when compared with wild-type control. MiR-155 deficiency results in significantly decrease in IL-17A expression both in vivo and in vitro. And the increased expression of WT-1, nephrin, and ac-nephrin was reversed with additional treatment of rmIL-17. Furthermore, we found that the inhibited Th17 differentiation induced by miR-155 deficiency was dependent on increased expression of SOCS1. In conclusion, miR-155 deficiency promotes nephrin acetylation and attenuates renal damage in hyperglycemia-induced nephropathy. This was associated with inhibited IL-17 production through enhancement of SOCS1 expression.