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Acute Effects of Cigarette Smoke Extract on CXC Chemokines and Matrix Metalloproteinases Released by Airway Epithelial Cells

Temple University School of Medicine, Philadelphia, Pennsylavnia

Correspondence and requests for reprints should be addressed to Steven G. Kelsen, Temple University School of Medicine, Lab #4, 10th Floor, Parkinson Pavilion, TUH, 3401 N. Broad Street, Philadelphia, PA 19140. E-mail kelsen{at}temple.edu

Chronic cigarette smoking may cause airway inflammation and remodeling, in part by affecting chemokine and matrix metalloproteinase release by airway epithelial cells. The acute effects of cigarette smoking on chemokine and matrix metalloproteinase (MMP) release are unstudied, however. We examined the effect of acute exposure to cigarette smoke extract (CSE) on the release of chemokines, IFN- inducible protein of 10 (IP-10) and IL-8, and the MMPs, MMP-1, MMP-2, MMP-9, by cultured normal human bronchial epithelial cells (NHBEC). CSE from two research cigarettes (2R4) was prepared by bubbling smoke into cell culture medium. Cultured NHBEC were exposed to 0, 7.5, 15, or 22.5% CSE for 24 h (n = 4 experiments). IP-10 and IL-8 protein levels in cell-conditioned medium were measured by flow cytometry using a cytometric bead array. MMP-1, -2, and -9 were measured by ELISA. CSE at 0, 7.5, and 15% had no effect on cell viability, while 22.5% decreased viability by 10%. CSE affected chemokine and MMP expression in a concentration-dependent fashion. Specifically, at 22.5% CSE, IP-10 protein decreased to 24% of control (p = 0.008). In contrast, IL-8 increased to 305% of control (p = 0.036). CSE at 22.5% increased MMP-1 to 411% of control (p = 0.005), but inhibited MMP-2 and -9 protein to 62% and 44% of control, respectively (p = 0.01 for both). The inhibitor of MMPs, TIMP-1, was unchanged. mRNA expression assessed by real-time RT-PCR changed in the same direction as the protein expression. In NHBEC, acute exposure to CSE differentially regulates the chemokines responsible for recruitment into the airway of Th1 lymphocytes (IP-10) and neutrophils (IL-8) and the metalloproteinases (MMP-1, -2, and -9) responsible for degradation of basement membrane collagen. The effect of these complex changes on the processes important for the development of COPD remains to be determined.

FOOTNOTES

Conflict of Interest Statement: T.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.O.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.J. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Y.Y. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.G.K. has been paid $6,000 by GlaxoSmithKline for serving on Advisory Boards and a grant to study COPD. He has also received $4,000 from Novartis for several lectures.

(Received in original form March 17, 2006; accepted in final form March 28, 2006)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gaddapara, T. Articles by Kelsen, S. G. Search for Related Content PubMed Articles by Gaddapara, T. Articles by Kelsen, S. G.