ABSTRACT
no abstract available.
ABSTRACT
BACKGROUND: Allergic contact dermatitis (ACD), which is accelerated by interferon (IFN)-γ and suppressed by interleukin (IL)-10 as regulators, is generally self-limited after removal of the contact allergen. Adipose tissue-derived multipotent mesenchymal stem cells (ASCs) potentially exert immunomodulatory effects. Considering that subcutaneous adipose tissue is located close to the site of ACD and includes mesenchymal stem cells (MSCs), the MSCs in adipose tissue could contribute to the self-limiting course of ACD. OBJECTIVE: The aims of the present study were to elucidate the effects of MSCs in adipose tissue on ACD and to examine any cytokine-mediated mechanisms involved. METHODS: Ear thickness in a C57BL/6 mouse model of ACD using contact hypersensitivity (CHS) elicited by 2,4,6-trinitro-1-chlorobenzene was evaluated as a marker of inflammation level. Five and nine mice were injected with ASCs and phosphate-buffered saline (PBS), respectively. After ASC or PBS injection, real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed. RESULTS: Histology showed that CHS was self-limited and ear thickness was suppressed by ASCs in a dose-dependent manner. IFN-γ expression in the elicited skin site and regional lymph nodes was significantly lower in ASC-treated mice than in control mice. IL-10 expression did not differ between treated and control mice. The suppressive effects of ASCs on CHS response did not differ between IL-10 knock-out C57BL/6 mice and wild-type mice. CONCLUSION: The present findings suggest that MSCs in adipose tissue may contribute to the self-limiting course of ACD through decreased expression of IFN-γ, but not through increased expression of IL-10.
Subject(s)
Animals , Mice , Adipose Tissue , Dermatitis, Allergic Contact , Dermatitis, Contact , Ear , Enzyme-Linked Immunosorbent Assay , Inflammation , Interferons , Interleukin-10 , Interleukins , Lymph Nodes , Mesenchymal Stem Cells , Picryl Chloride , Skin , Subcutaneous FatABSTRACT
BACKGROUND: CC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)-alpha- and interferon (IFN)-gamma-induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes. OBJECTIVE: To identify the mechanism underlying CCL22 production by HaCaT cells. METHODS: We investigated the signal transduction pathways by which TNF-alpha and IFN-gamma stimulate HaCaT cells to produce CCL22 by adding various inhibitors. RESULTS: TNF-alpha- and IFN-gamma-induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitor II, and Janus kinase (JAK) inhibitor 1. CONCLUSION: Our results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells.
Subject(s)
Humans , Bays , Cell Line , Chemokine CCL17 , Chemokine CCL22 , Interferons , JNK Mitogen-Activated Protein Kinases , Keratinocytes , Ligands , p38 Mitogen-Activated Protein Kinases , Phosphotransferases , Protein Kinases , ErbB Receptors , Signal Transduction , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Pruritis caused by atopic dermatitis (AD) is not always well controlled by topical corticosteroid therapy, but use of tacrolimus often helps to soothe such intractable pruritis in clinical settings. OBJECTIVE: To determine the anti-pruritic efficacy of topical tacrolimus in treating AD in induction and maintenance therapy. METHODS: Prior to the study, patients were randomly allocated into two groups, induction therapy followed by tacrolimus monotherapy maintenance, and induction therapy followed by emollient-only maintenance. In the induction therapy, the patients were allowed to use topical tacrolimus and emollients in addition to a low dose (<10 g/week) of topical steroids. Patients showing relief from pruritis were allowed to proceed to maintenance therapy. Recurrence of pruritis in maintenance therapy was examined as a major endpoint. RESULTS: Two-thirds of patients (44/68; 64.7%) showed relief from pruritis after induction therapy. Pruritis recurred in 23.8% (5/21) of the tacrolimus monotherapy group and in 100% (21/21) of the emollient group during maintenance period, a difference that was statistically significant. CONCLUSION: Use of topical tacrolimus is effective in controlling pruritis of AD compared to emollient.