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.

Abstract

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.

• Authors: Sang Jae Bae, Jeong-Beom Lee, Kazuhiro Shimizu, Yutaka Kuwazuka
• Journal: Immunological investigations (Immunol Invest) Vol. 39 Issue 2 Pg. 93-102 (Jan 2010) ISSN: 1532-4311 [Electronic] England
• PMID: 20136617 (Publication Type: Journal Article)

Chemical References

• Anti-Allergic Agents
• Arylsulfonates
• CCL11 protein, human
• Chemokine CCL11
• Chemotactic Factors, Eosinophil
• RNA, Messenger
• Sulfonium Compounds
• Transforming Growth Factor beta
• Interleukin-4
• suplatast tosilate

Topics

• Anti-Allergic Agents (pharmacology)
• Arylsulfonates (pharmacology)
• Asthma (drug therapy, immunology)
• Cells, Cultured
• Chemokine CCL11 (antagonists & inhibitors, biosynthesis)
• Chemotactic Factors, Eosinophil (antagonists & inhibitors, biosynthesis)
• Dose-Response Relationship, Drug
• Drug Synergism
• Enzyme-Linked Immunosorbent Assay
• Fibroblasts (drug effects, immunology, metabolism)
• Gene Expression Regulation
• Humans
• Interleukin-4 (pharmacology)
• Polymerase Chain Reaction
• RNA, Messenger (antagonists & inhibitors, biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Skin (cytology)
• Sulfonium Compounds (pharmacology)
• Transforming Growth Factor beta (pharmacology)
• Up-Regulation