Cigarette smoke inhibits airway epithelial cell innate immune responses to bacteria.
The human upper respiratory tract, including the nasopharynx, is colonized by a diverse array of microorganisms. While the host generally exists in harmony with the commensal microflora, under certain conditions, these organisms may cause local or systemic disease. Respiratory epithelial cells act as local sentinels of the innate immune system, responding to conserved microbial patterns through activation of signal transduction pathways and cytokine production. In addition to colonizing microbes, these cells may also be influenced by environmental agents, including cigarette smoke (CS). Because of the strong relationship among secondhand smoke exposure, bacterial infection, and sinusitis, we hypothesized that components in CS might alter epithelial cell innate immune responses to pathogenic bacteria. We examined the effect of CS condensate (CSC) or extract (CSE) on signal transduction and cytokine production in primary and immortalized epithelial cells of human or murine origin in response to nontypeable Haemophilus influenzae and Staphylococcus aureus. We observed that epithelial production of interleukin-8 (IL-8) and IL-6 in response to bacterial stimulation was significantly inhibited in the presence of CS (P < 0.001 for inhibition by either CSC or CSE). In contrast, epithelial production of beta interferon (IFN-beta) was not inhibited. CSC decreased NF-kappaB activation (P < 0.05) and altered the kinetics of mitogen-activated protein kinase phosphorylation in cells exposed to bacteria. Treatment of CSC with antioxidants abrogated CSC-mediated reduction of epithelial IL-8 responses to bacteria (P > 0.05 compared to cells without CSC treatment). These results identify a novel oxidant-mediated immunosuppressive role for CS in epithelial cells.
Kulkarni
Ritwij
R
Department of Pediatrics, Columbia University, 650 West 168th Street (BB 443), New York, NY 10032, USA.
Rampersaud
Ryan
R
Aguilar
Jorge L
JL
Randis
Tara M
TM
Kreindler
James L
JL
Ratner
Adam J
AJ
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D016899:Interferon-beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke; D013211:Staphylococcus aureus / Q000276:immunology*
D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012906:Smoke; D016899:Interferon-beta; D020928:Mitogen-Activated Protein Kinases