title: Corticosteroid and cytokines synergistically enhance toll-like receptor 2 expression in respiratory epithelial cells.
abstract: Respiratory epithelial cells play important roles not only in host defense mechanisms, but also in inflammatory responses. Inhaled corticosteroids are widely used for the treatment of patients with inflammatory lung disorders, including asthma, chronic obstructive pulmonary disease, and sarcoidosis. Corticosteroids effectively reduce the production of inflammatory mediators, such as cytokines and chemokines. Although these molecules are also essential for host defense responses, there is no convincing evidence that inhaled corticosteroids increase susceptibility to lower respiratory tract infections. To test the involvement of Toll-like receptor (TLR) family molecules in this phenomenon, we examined the effects of various cytokines and corticosteroid on the expression of TLRs in human respiratory epithelial cells. Among the TLRs tested, TLR2 expression was significantly enhanced after stimulation with a combination of tumor necrosis factor-alpha and interferon-gamma. Dexamethasone synergistically enhanced TLR2 expression in combination with tumor necrosis factor-alpha and interferon-gamma in terms of both mRNA and protein levels. Furthermore, increased cell-surface TLR2 was functional, judging from the remarkable induction of interleukin-6, interleukin-8, and beta-defensin-2 after stimulation with peptidoglycan. These results provide evidence for a novel function of corticosteroids in airway inflammatory disorders, and indicate that the use of inhaled corticosteroids in such disorders may have a beneficial role in host defense mechanisms.
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Homma
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Noriko
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Jonathan
authors.initials: J
authors.lastname: Batchelor
authors.forename: Mamoru
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Shosuke
authors.initials: S
authors.lastname: Imai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakiguchi
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage; D004357:Drug Synergism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D023083:beta-Defensins / Q000378:metabolism
chemical_list: C106641:DEFB4A protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D003907:Dexamethasone; D007371:Interferon-gamma