Increase effect of transforming growth factor on eotaxin production by normal cultured dermal fibroblasts stimulated with interleukin-4: inhibitory effect of suplatast tosilate on eotaxin production.
Eotaxin plays a central role in the development of allergic disease, including atopic dermatitis, asthma, and nasal allergy. Interleukin (IL)-4 induces eotaxin production in normal human dermal fibroblasts. On the other hands, Transforming growth factor-beta (TGF-beta), a multifunctional regulatory cytokine, affects many biological functions, including fibroblast growth and differentiation and Th2 cytokine regulation. In this study, we investigated the effect of TGF-beta on IL-4-induced eotaxin production by normal human fibroblasts, as well as the effect of suplatast tosilate, an antiallergic drug that selectively inhibits Th2 cytokine production. Dermal fibroblast treatment with IL-4 and TGF-beta for 24 h increased eotaxin production and expression of eotaxin mRNA, as measured by enzyme-linked immunosorbent assay (ELISA) and reverse-transcriptase polymerase chain reaction (RT-PCR), respectively. TGF-beta synergistically up-regulated eotaxin production and eotaxin mRNA expression when stimulated with IL-4. Suplatast tosilate dose-dependently inhibited eotaxin production induced by IL-4 or IL-4 plus TGF-beta. These results suggest that TGF-beta may regulate skin allergic inflammation by up-regulating eotaxin production in dermal fibroblasts. Suplatast tosilate might suppress this inflammation by inhibiting eotaxin production.
Department of Dermatology, Nagasaki University, School of Medicine, Nagasaki, Japan.
Sang Jae
SJ
Bae
Jeong-Beom
JB
Lee
Kazuhiro
K
Shimizu
Yutaka
Y
Kuwazuka
D018926:Anti-Allergic Agents / Q000494:pharmacology; D001190:Arylsulfonates / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002631:Chemotactic Factors, Eosinophil / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology; D013452:Sulfonium Compounds / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation
D018926:Anti-Allergic Agents; D001190:Arylsulfonates; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D002631:Chemotactic Factors, Eosinophil; D012333:RNA, Messenger; D013452:Sulfonium Compounds; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; C073028:suplatast tosilate