Modulation of expression and function of Toll-like receptor 3 in A549 and H292 cells by histamine.
It was reported recently that histamine induced Toll-like receptor (TLR)2 and TLR4 expression in endothelial cells and enhanced their sensitivity to Gram-positive and Gram-negative bacteria; and that TLRs were expressed in airway epithelial cells and that several inflammatory mediators modulated their expression. However, little is known of potential influence of histamine on TLRs in pulmonary epithelial cells. In the present study, effects of histamine on expression of TLRs in both human A549 and NCI-H292 cell lines were examined by using real-time quantitative RT-PCR analysis, flow cytometry and immunofluorescent staining. The results revealed that both cell types constitutively expressed mRNAs for TLR1-TLR10. Histamine up-regulated the expression of TLR3 mRNA by 12.3- and 11.6-fold, respectively in both cell types. The time course showed that histamine induced TLR3 mRNA expression was initiated at 30 min, nearly reached peak levels after 2 h and was sustained at least until 12 h. Histamine also induced TLR3 protein expression in A549 and NCI-H292 cells. Histamine and poly (I:C), a specific TLR3 ligand stimulated interleukin (IL)-8 secretion from both cell types. Moreover, histamine enhanced poly (I:C)-induced IL-8 secretion and phosphorylation of NF-kappaB in the two cell types, and histamine H1 receptor antagonists inhibited the action of histamine. In conclusion, histamine selectively up-regulated expression of TLR3, and stimulated IL-8 secretion from the cells. Histamine also enhanced poly (I:C) induced IL-8 secretion and phosphorylation of NF-kappaB. These observations suggest that histamine might play an important role in enhancing the innate immune responses of airway to viral infection.
Hou
Yi-Feng
YF
Allergy and Inflammation Research Institute, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515041, China.
Zhou
Yan-Chun
YC
Zheng
Xiao-Xuan
XX
Wang
Hai-Yan
HY
Fu
Yi-Ling
YL
Fang
Zhe-Man
ZM
He
Shao-Heng
SH
D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006632:Histamine / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D007700:Kinetics; D016328:NF-kappa B / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051196:Toll-Like Receptor 3 / Q000032:analysis / Q000235:genetics / Q000276:immunology*
D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D006632:Histamine; D011070:Poly I-C