Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts.
Eicosanoids are lipid-signaling mediators released by many cells in response to various stimuli. Increasing evidence suggests that eicosanoids such as leukotrienes and prostaglandins (PGs) may directly mediate remodeling. In this study, we assessed whether these substances could alter extracellular matrix (ECM) proteins and the inflammatory profiles of primary human airway smooth muscle cells (ASM) and fibroblasts. PGE(2) decreased both fibronectin and tenascin C in fibroblasts but only fibronectin in ASM. PGD(2) decreased both fibronectin and tenascin C in both ASM and fibroblasts, whereas PGF(2α) had no effect on ECM deposition. The selective PGI(2) analog, MRE-269, decreased fibronectin but not tenascin C in both cell types. All the PGs increased IL-6 and IL-8 release in a dose-dependent manner in ASM and fibroblasts. Changes in ECM deposition and cytokine release induced by prostaglandins in both ASM and fibroblasts were independent of an effect on cell number. Neither the acute nor repeated stimulation with leukotrienes had an effect on the deposition of ECM proteins or cytokine release from ASM or fibroblasts. We concluded that, collectively, these results provide evidence that PGs may contribute to ECM remodeling to a greater extent than leukotrienes in airway cells.
Respiratory Research Group, Cell Biology, Woolcock Institute of Medical Research, PO Box M77, Missenden Rd., Camperdown NSW 2050 Australia. dvan7422@gmail.com
David
D
Van Ly
Janette K
JK
Burgess
Thomas G
TG
Brock
Tak H
TH
Lee
Judith L
JL
Black
Brian G G
BG
Oliver
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020126:Brefeldin A / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019063:Tenascin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D055815:Young Adult
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D015850:Interleukin-6; D016209:Interleukin-8; D015289:Leukotrienes; D011453:Prostaglandins; D011500:Protein Synthesis Inhibitors; D019063:Tenascin; D016212:Transforming Growth Factor beta; D020126:Brefeldin A