The effects of wheel-running using the upper limbs following immobilization after inducing arthritis in the knees of rats.

This study investigated the effects of wheel-running using the upper limbs following immobilization after inducing arthritis in the knees of rats. Forty male Wistar rats (aged 8 weeks) divided into four groups randomly: arthritis (AR), immobilization after arthritis (Im), wheel-running exercise with the upper limbs following immobilization after arthritis induction (Im+Ex) and sham arthritis induction (Con). The knee joints of the Im and Im+Ex groups were immobilized with a cast for 4 weeks. In the Im+Ex group, wheel-running exercise was administered for 60 min/day (5 times/week). The swelling and the pressure pain threshold (PPT) of the knee joint were evaluated for observing the condition of inflammatory symptoms in affected area, and the paw withdraw response (PWR) was evaluated for observing the condition of secondary hyperalgesia in distant area. Especially, in order to evaluate histological inflammation in the knee joint, the number of macrophage (CD68-positive cells) in the synovium was examined. The expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn (L2-3 and L4-5) was examined to evaluate central sensitization. The Im+Ex group showed a significantly better recovery than the Im group in the swelling, PPTs, and PWRs. Additionally, CGRP expression of the spinal dorsal horn (L2-3 and L4-5) in the Im+Ex group was significantly decreased compared with the Im group. According to the results, upper limb exercise can decrease pain in the affected area, reduce hyperalgesia in distant areas, and suppress the central sensitization in the spinal dorsal horn by triggering exercise-induced hypoalgesia (EIH).

Detection of cerebrospinal fluid leakage: initial experience with three-dimensional fast spin-echo magnetic resonance myelography.

BACKGROUND: The pathogenesis of cerebrospinal fluid (CSF) hypovolemia is supposed to be caused by CSF leakage through small dural defects. PURPOSE: To compare source three-dimensional (3D) fast spin-echo (FSE) images of magnetic resonance (MR) myelography with radionuclide cisternography findings, and to evaluate the feasibility of MR myelography in the detection of CSF leakage. MATERIAL AND METHODS: A total of 67 patients who were clinically suspected of CSF hypovolemia underwent indium-111 radionuclide cisternography, and 27 of those who had direct findings of CSF leakage were selected for evaluation. MR myelography with 3D FSE sequences (TR/TE 6000/203 ms) was performed at the lumbar spine for all patients. We evaluated source images and maximum intensity projection (MIP) images of MR myelography, and the findings were correlated with radionuclide cisternography findings. MR myelography of five healthy volunteers was used as a reference. The MR visibility of the CSF leakage was graded as definite (leakage clearly visible), possible (leakage poorly seen), or absent (not shown). RESULTS: CSF leakage was identified with source 3D FSE images in 22 (81.5%) of 27 patients. Of the 22 patients, 16 were graded as definite and six were graded as possible. For the definite cases, 3D FSE images clearly showed the extent of the leaked CSF in the paraspinal structures. In the remaining five patients with absent findings, radionuclide cisternography showed only slight radionuclide activity out of the arachnoid space. CONCLUSION: Source 3D FSE images of MR myelography seem useful in the detection of CSF leakage. Invasive radionuclide cisternography may be reserved for equivocal cases only.

IL-4 and IL-13 induce myofibroblastic phenotype of human lung fibroblasts through c-Jun NH2-terminal kinase-dependent pathway.

BACKGROUND: Myofibroblasts play a role in the airway remodeling response of bronchial asthma. IL-4 and IL-13 are possibly involved in the airway remodeling response by inducing extracellular matrix production by fibroblasts. However, the roles of these cytokines in inducing the phenotypic modulation of human lung fibroblasts (HLFs) to myofibroblasts and the intracellular signal have not been determined. OBJECTIVE: We examined the effect of IL-4 and IL-13 on inducing the phenotypic modulation of HLFs to myofibroblasts characterized by alpha-smooth muscle actin and examined the role of the mitogen-activated protein (MAP) kinase superfamily in inducing the myofibroblastic phenotype of the HLF to clarify these issues. METHODS: Phosphorylation and activities of c-Jun NH(2)-terminal kinase (JNK), p38 MAP kinase, and extracellular signal-regulated kinase (Erk) were examined by using Western blotting and in vitro kinase assay. Expression of alpha-smooth muscle actin in IL-4- and IL-13-stimulated HLFs was analyzed by means of Western blotting. RESULTS: The results showed that (1) IL-4 and IL-13 increased alpha-smooth muscle actin expression in a dose- and time-dependent manner; (2) IL-4 and IL-13 induced increases in JNK and Erk phosphorylation and activity but not p38 MAP kinase activity; (3) CEP-1347 and PD 98059 attenuated IL-4- and IL13-induced JNK and Erk activity, respectively; and (4) CEP-1347, but not PD 98059, attenuated IL-4- and IL-13-induced alpha-smooth muscle actin expression. CONCLUSION: These results indicate that IL-4 and IL-13 are capable of inducing the phenotypic modulation of HLFs to myofibroblasts, and JNK, but not p38 MAP kinase and Erk, regulates IL-4- and IL-13-induced phenotypic modulation of HLFs to myofibroblasts.

Nerve cell tumours of the cerebrum: variable clinical and pathological manifestations.

Nerve cell tumours of the cerebrum tend to display a high degree of morphological variability from case to case, and this leads to poor understanding of these tumours. We retrospectively reviewed the clinical and patho-anatomic features of 16 primary nerve cell tumours of the cerebrum (M:9; F:7; average age at onset: 10.2 years). Intraventricular tumours were not included. In 13 patients epileptic seizures were the only symptoms, while three had headache or hemiparesis. Seven tumours were located in the frontal lobe, four in the parietal lobe, two in the temporal lobe and one each in the fronto-parietal lobes, occipital lobe and the midbrain. Tumours were histologically classified into three groups. In the first group, six tumours had the morphological features of classic gangliocytoma or ganglioglioma. In the second group six cerebral and midbrain tumours were composed of small cells, which showed apparent neuronal differentiation including positive immunoreactivity for synaptophysin and the presence of synaptic structures. These tumours usually involved both the cortex and white matter. In the third group, three tumours were composed of small nerve cells and ganglioid cells. All tumours were relatively well circumscribed, and thus eight tumours were totally removed, five subtotally and three partially. Following surgery, three patients, except one, are alive with stable imaging findings for 4 months - 19.3 years (average 11.6 years) after treatment. While small nerve cell tumours are found throughout the cerebrum and its identification broadens the spectrum of neuronal and mixed neuro-glial tumours, most of these tumours are biologically indolent.

Pituitary tumours in adolescence: clinical behaviour and neuroimaging features of seven cases.

The clinicopathologic features of seven paediatric patients with pituitary adenomas (2 male, 5 female; mean age 14.3 years) were reviewed. There were three non-functioning adenomas, three prolactinomas, and one growth hormone producing adenoma. Five patients presented with visual field deficits, and six patients had endocrine symptoms, which included menstrual irregularities in all female patients, pubertal delay in two females, and growth delay and gigantism in one case each. On neuroimaging studies, five adenomas showed parasellar extension, while the remaining two prolactinomas were intrasellar microadenomas. While two patients with prolactinomas received good results with bromocriptine treatment alone, the remaining five patients underwent either craniotomy or transsphenoidal surgery. Postoperatively, visual disturbances improved markedly in all patients. Two patients also received replacement hormonal therapy. While six patients have been stable for 3.6 years on average, one non-functioning tumour recurred 2 years after the initial transcranial subtotal resection of the tumour. Although there are still many unknowns concerning the biology and optimal treatments for paediatric pituitary adenomas, many of them are assumed to be relatively rapidly growing tumours, while others merely have an earlier tumour genesis than in adults.

Multi-level disruption of the spinal nerve root sleeves in spontaneous spinal cerebrospinal fluid leakage--two case reports.

A 37-year-old male and an 18-year-old male presented with spontaneous spinal cerebrospinal fluid (CSF) leakage from multiple nerve root sleeves. Both patients suffered abrupt onset of intense headache followed by nausea, dizziness, and one patient with and one without positional headache. Radioisotope spinal cisternography of both patients revealed that the CSF leaks were not localized in a special zone but distributed to multiple spinal nerve root sleeves. Magnetic resonance (MR) myelography suggested that the spinal CSF column was fully expanded to the root sleeves. The extraspinal nerve bundles demonstrated numerous high intensity spots. Both patients were treated conservatively, and their symptoms resolved within one month. Repeat radioisotope cisternography and MR myelography confirmed the spine was normal after recovery. We suggest that spreading disruption of the arachnoid membrane occurs at the nerve root sleeves due to CSF overflow into the spinal canal.

Inverting papilloma of the sphenoid sinus: report of two cases.

Two patients with sphenoid sinus inverting papilloma who were treated either by transcranial or sublabial trans-septal approach are reported. Inverting papillomas arising from the sphenoid sinus are exceedingly rare. The clinical and neuro-imaging features, as well as surgical treatment, for sphenoid sinus tumours are also briefly discussed.

Intracellular glutathione regulates tumour necrosis factor-alpha-induced p38 MAP kinase activation and RANTES production by human bronchial epithelial cells.

BACKGROUND: RANTES plays an important role in the production of allergic inflammation of the airway through its chemotactic activity for eosinophils. The cellular reduction and oxidation (redox) changes are involved in the activation of p38 mitogen-activated protein (MAP) kinase and the induction of cytokine expression. It has previously been shown that tumour necrosis factor (TNF)-MA activates p38 mitogen-activated protein (MAP) kinase to produce cytokine, including RANTES, that N-acetylcysteine (NAC) attenuates cytokine production by human bronchial epithelial cells (BECs), and that sensitivity to TNFalpha is inversely correlated with cellular redox state. However, a role of cellular redox regulated by intracellular glutathione (GSH) in TNFalpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated RANTES production by human BECs has not been determined. OBJECTIVE: Human BECs were exposed to NAC or buthionine sulfoximine (BSO). TNFalpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated RANTES production by human BECs were then examined in order to clarify these issues. RESULTS: The results showed that: NAC attenuated TNFalpha-induced p38 MAP kinase activation and RANTES production; SB 203580 as the specific inhibitor of p38 MAP kinase activity attenuated TNF-alpha-induced RANTES production; BSO facilitated TNF-alpha-induced p38 MAP kinase activation and RANTES production; SB 203580 attenuated BSO-mediated facilitation of TNF-alpha-induced RANTES production; and the intracellular GSH increased in NAC-treated cells, whereas the intracellular GSH was reduced in BSO-treated cells. CONCLUSIONS: These results indicate that cellular redox regulated by GSH is critical for TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated RANTES production by human BECs.

[Teratoma in the cerebellar hemisphere of an infant].

We report here a 4-month-old male infant with a cerebellar teratoma. After vomiting for 5 days, he had a tonic-clonic seizure on the left showing secondary generalization. Neuroimaging studies showed severe hydrocephalus and a large tumor in the left cerebellar hemisphere, which showed calcification. Postictal scalp electroencephalogram showed right hemispheric spikes and spike-waves. He underwent an emergency operation and had the tumor totally removed. Histological diagnosis of the tumor was immature teratoma. Intracranial teratomas have a predilection for supratentorial and midline sites. They are the most common in the neonatal period. We presented a very rare case of teratoma in the cerebellar hemisphere of an infant.

Transforming growth Factor-beta1 induces phenotypic modulation of human lung fibroblasts to myofibroblast through a c-Jun-NH2-terminal kinase-dependent pathway.

Myofibroblasts play an important role in the fibrogenic process of pulmonary fibrosis. Transforming growth factor (TGF)-beta is well known to induce the phenotypic modulation of fibroblasts to myofibroblasts; however, the intracellular signal regulating induction of the myofibroblastic phenotype of human lung fibroblasts (HLF) has not been determined. In the present study, we examined the role of the mitogen-activated protein kinase (MAPK) superfamily in inducing the phenotypic modulation of HLF to myofibroblasts characterized by alpha-smooth-muscle actin expression, in order to clarify this issue. The results showed that: (1) TGF-beta1 caused the phenotypic modulation of HLF to myofibroblasts in a dose- and a time-dependent manner; (2) TGF-beta1 induced increases in c-Jun-NH2- terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (Erk) phosphorylation and activity; (3) the inhibitors CEP-1347, SB 203580, and PD 98059 attenuated TGF-beta1-induced JNK, p38 MAPK, and Erk activity, respectively; and (4) CEP-1347, but not SB 203580 or PD 98059, attenuated the TGF-beta1-induced phenotypic modulation of HLF to myofibroblasts in a dose-dependent manner. These results indicate that TGF-beta1 is capable of inducing the myofibroblastic phenotype of HLF, and that JNK regulates the phenotypic modulation of TGF-beta1-stimulated HLF to myofibroblasts.

[A case of recurrent convexity meningioma with malignant transformation 26 years after total tumor removal].

Meningiomas are common intracranial tumors, the majority of which are considered benign. However, they sometimes show altered biologic behavior, associated with local aggressiveness and late distant metastasis. We report a patient with a convexity meningioma, which recurred as a malignant transformation 26 years after a total tumor removal. A 75-year-old man was transferred to a local hospital because of general convulsions and left hemiparesis. The patient had had an operation for the total removal of a right frontal convexity meningioma at the age of 46 and had been free of its effects until the age of 72. Brain magnetic resonance imaging (MRI) showed a recurrent tumor located in the anterior area of the previous craniotomy. Over the following two and a half years, MRI revealed rapid enlargement and infiltration of the tumor into the brain parenchyma. The primary tumor was nodular, macroscopically well demarcated from the surrounding brain tissue and, histologically, was a transitional type of meningioma without any atypical features. In contrast, the recurrent tumor, whose border was ill-defined, had invaded the neighboring brain. A histological specimen of the recurrent tumor showed highly malignant features such as necrosis, intracerebral infiltration, dense cellularity, and high proliferating activity as demonstrated by a cell kinetic study using the MIB 1 staining index. We should be mindful that recurrence from common benign type meningiomas may occur as malignant transformations after more than two decades.

N-acetylcysteine attenuates TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells.

1. We have previously shown that tumour necrosis factor-alpha (TNF-alpha) activates p38 mitogen-activated protein (MAP) kinase to produce interleukin-8 (IL-8) by human pulmonary vascular endothelial cells. Reactive oxygen species (ROS) including H(2)O(2) generated by TNF-alpha can act as signalling intermediates for cytokine induction; therefore, scavenging ROS by anti-oxidants is important for the regulation of cytokine production. However, the effect of N-acetylcysteine (NAC), which acts as a precursor of glutathione (GSH) synthesis, on TNF-alpha-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined. To clarify these issues, we examined the effect of NAC on TNF-alpha-induced activation of p38 MAP kinase, MAP kinase kinase (MKK) 3 and MKK6 which are upstream regulators of p38 MAP kinase, and p38 MAP kinase-mediated IL-8 production. 2. Human pulmonary vascular endothelial cells that had been preincubated with NAC were stimulated with TNF-alpha and then the activation of p38 MAP kinase and MKK3/MKK6 in the cells and IL-8 concentrations in the culture supernatants were determined. 3. Intracellular GSH levels increased in NAC-treated cells. 4. NAC attenuated TNF-alpha-induced activation of p38 MAP kinase and MKK3/MKK6. 5. NAC attenuated p38 MAP kinase-mediated IL-8 production by TNF-alpha-stimulated cells. 6. These results indicate that the cellular reduction and oxidation (redox) regulated by intracellular GSH is critical for TNF-alpha-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells, and we emphasize that anti-oxidant therapy is an important strategy for the treatment of acute lung injury.

Inhalant corticosteroids inhibit hyperosmolarity-induced, and cooling and rewarming-induced interleukin-8 and RANTES production by human bronchial epithelial cells.

Inhaled corticosteroids are widely used for the treatment of bronchial asthma, and a long-term treatment with inhaled corticosteroids is effective in preventing exercise-induced bronchoconstriction (EIB). We have previously shown that hyperosmolarity, and cooling and rewarming induced interleukin-8 (IL-8) expression in human bronchial epithelial cells (BEC). However, the effect of inhalant corticosteroids on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production has not been determined. To clarify these issues, we examined the effect of inhalant corticosteroids, beclomethasone dipropionate (BDP), and budesonide (BUD) on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. The results showed that BDP and BUD inhibited hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. Because our previous studies have shown that p38 mitogen-activated protein (MAP) kinase and c-Jun-NH(2)-terminal kinase (JNK) regulate hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production, we examined the effect of BDP and BUD on p38 MAP kinase and JNK activation. The results showed that BDP and BUD did not inhibit hyperosmolarity-induced and cooling-induced p38 MAP kinase and JNK activation. These results indicated that inhalant corticosteroids inhibited hyperosmolarity-, and cooling and rewarming-induced IL-8 and RANTES production; however, the mechanism of inhaled corticosteroid-mediated inhibition of hyperosmolarity-induced, and cooling and rewarming- induced cytokine production remains to be clarified.

[Medulloblastoma with neuronal differentiation: a report of five cases].

This report presents a retrospective analysis of 5 patients who were treated for cerebellar medulloblastoma with neuronal differentiation. Four males and 1 female ranged in age from 6 months to 9 years at the time of diagnosis. Total removal of the tumor was achieved in 3 patients, and partial removal in 2. While these tumors were composed of small cells and had regions resembling desmoplastic medulloblastoma, they in part showed neuronal characteristics which included parallel row or linear array arrangements of tumor cells in an eosinophilic fibrillary matrix. Postoperatively, 3 patients received craniospinal radiation therapy, one received local radiation to the primary site, and the remaining one received only systemic chemotherapy. During the follow-up period of 3.8-25.2 years, 4 patients have been in continuous remission with mild to moderate neurological deficits, while the remaining one died 3.9 years after surgery. The clinical and anatomic pathological features of medulloblastomas with neuronal differentiation are reviewed while the therapeutic problems associated with these tumors are also discussed.

Regulation by intracellular glutathione of TNF-alpha-induced p38 MAP kinase activation and RANTES production by human pulmonary vascular endothelial cells.

BACKGROUND: We have previously shown that p38 mitogen-activated protein (MAP) kinase regulates tumor necrosis factor-alpha (TNF-alpha)-induced RANTES production by human pulmonary vascular endothelial cells, and that sensitivity to TNF-alpha is inversely correlated with cellular reduction and oxidation (redox) state. However, a regulatory role of intracellular glutathione (GSH) in TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated RANTES production has not been determined. In the present study, therefore, we extended our previous studies and focused on redox regulation on p38 MAP kinase activation. METHODS: Human pulmonary vascular endothelial cells were exposed to N-acetylcysteine (NAC) or buthionine sulfoximine (BSO), and then TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated RANTES production were determined. RESULTS: The results showed that 1) NAC attenuated TNF-alpha-induced p38MAP kinase activation and RANTES production 2) SB 203580 as the specific inhibitor of p38 MAP kinase activity attenuated TNF-alpha-induced RANTES production 3) BSO facilitated TNF-alpha-induced p38 MAP kinase activation and RANTES production 4) SB 203580 attenuated BSO-mediated facilitation of TNF-alpha-induced RANTES production. CONCLUSIONS: These results indicated that TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated RANTES production by human pulmonary vascular endothelial cells are inversely regulated by intracellular GSH levels.

Selective inhibitor of p38 mitogen-activated protein kinase inhibits lipopolysaccharide-induced interleukin-8 expression in human pulmonary vascular endothelial cells.

Adult respiratory distress syndrome (ARDS) characterized by permeability edema is observed in severe insults such as bacteremia sepsis. Interleukin (IL)-8, which chemoattracts and activates neutrophils, has been suggested to play an important role in the production of ARDS. Therefore, the inhibition of IL-8 production is an important strategy for the treatment of ARDS. Recent studies have revealed the role of p38 mitogen-activated protein (MAP) kinase in cytokine expression and the inhibition by a selective inhibitor of p38 MAP kinase activity of cytokine expression in a variety of cell types. However, little is known about the role of p38 MAP kinase in lipopolysaccharide (LPS)-induced IL-8 expression in pulmonary vascular endothelial cells and the effect of a selective p38 MAP kinase inhibitor on it. In the present study, we therefore attempted to clarify these issues. The results showed that LPS induced p38 MAP kinase phosphorylation and activity, and SB 203580 as a selective inhibitor of p38 MAP kinase activity inhibited p38 MAP kinase activity and IL-8 expression in LPS-stimulated pulmonary vascular endothelial cells. These results indicate that p38 MAP kinase regulates LPS-induced IL-8 expression in pulmonary vascular endothelial cells. Although it is currently not known whether SB 203580 is capable of producing beneficial effects on ARDS, a strategy of inhibiting p38 MAP kinase activity by a selective p38 MAP kinase inhibitor may apply to the therapy for ARDS.

PAF-induced RANTES production by human airway smooth muscle cells requires both p38 MAP kinase and Erk.

Airway smooth muscle (ASM) cells, which have been regarded as having contractile properties in response to contractile inflammatory mediators, may also participate in airway inflammatory response by expressing various cytokines, including RANTES. However, the intracellular signal that regulates cytokine expression in ASM cells has not been determined. In the present study, we examined the role of p38 mitogen-activated protein (MAP) kinase and extracellular signal-regulated kinase (Erk) in RANTES production by ASM cells stimulated by platelet-activating factor (PAF) and tumor necrosis factor (TNF)-alpha. The results showed that PAF induced the threonine and tyrosine phosphorylation of p38 MAP kinase and Erk, and p38 MAP kinase and Erk activity. SB 203580 and PD 98059 almost completely inhibited p38 MAP kinase and Erk activity, respectively. SB 203580 and PD 98059 partially inhibited and acted additively to inhibit PAF-induced RANTES production. PAF also induced c-Jun-NH(2)-terminal kinase ( JNK) phosphorylation. TNF-alpha induced p38 MAP kinase and Erk phosphorylation, but neither SB 203580 nor PD 98059 inhibited RANTES production. These results indicate that both p38 MAP kinase and Erk involve RANTES production by ASM cells stimulated with PAF, but not TNF-alpha, and that the role of p38 MAP kinase and Erk in RANTES production by ASM cells appears to be stimulus-dependent.

Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation.

Air pollutants including diesel exhaust particles (DEPs) have been shown to enhance allergic responses. DEPs stimulate airway epithelial cells to produce various cytokines; however, the intracellular signal transduction pathway and the involvement of reduction and oxidation (redox) control in DEP-activated signaling have not been determined. In the present study, we therefore examined the role of p38 mitogen-activated protein (MAP) kinase in DEP-induced interleukin 8 (IL-8) and RANTES production by human bronchial epithelial cells (BECs) in order to clarify the intracellular signal transduction pathway that regulates IL-8 and RANTES production. In addition, we also examined the effect of a thiol-reducing agent, N-acetylcysteine (NAC), on DEP-induced p38 MAP kinase activation and cytokine production in order to clarify the redox control mechanism in DEP-induced p38 MAP kinase activation and IL-8 and RANTES production. The results showed that DEP induced IL-8 and RANTES production and the threonine and tyrosine phosphorylation of p38 MAP kinase, reflecting the activation of p38 MAP kinase in BECs. SB 203580, as the specific inhibitor of p38 MAP kinase activity, inhibited DEP-induced IL-8 and RANTES production. NAC inhibited DEP-induced p38 MAP kinase activation and IL-8 and RANTES production. These results indicate that p38 MAP kinase plays an important role in the DEP-activated signaling pathway that regulates IL-8 and RANTES production by BECs and that the cellular redox state is critical for DEP-induced p38 MAP kinase activation leading to IL-8 and RANTES production.