Th2 cytokine regulation of type I collagen gel contraction mediated by human lung mesenchymal cells.
Asthma is characterized by chronic inflammation of the airway wall with the presence of activated T helper 2 (Th2) lymphocytes. The current study assessed the ability of Th2 cytokines to modulate fibroblast-mediated contraction of collagen gels to determine if Th2 cytokines could contribute to tissue remodeling by altering mesenchymal cell contraction. Human fetal lung fibroblasts, human adult bronchial fibroblasts and human airway smooth muscle cells were cast into native type I collagen gels and allowed to contract in the presence or absence of IL (interleukin)-4, IL-5, IL-10, or IL-13. IL-4 and IL-13 but not IL-5 and IL-10 augmented collagen gel contraction in a concentration-dependent manner. Neither IL-4 nor IL-13 altered fibroblast production of transforming growth factor-beta or fibronectin. Both, however, decreased fibroblast prostaglandin (PG) E(2) release. Decreased PGE(2) release was associated with a decreased expression of cyclooxygenase 1 and 2 protein and mRNA. Indomethacin completely inhibited PGE(2) release and also augmented contraction. IL-4 and IL-13, however, added together with indomethacin further augmented contraction suggesting both a PGE-dependent and a PGE-independent effect. These findings suggest that IL-4 and IL-13 may modulate airway tissue remodeling and, therefore, could play a role in the altered airway connective tissue which characterizes asthma.
Liu
Xiangde
X
Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Kohyama
Tadashi
T
Wang
Hangjun
H
Zhu
Yun Kui
YK
Wen
Fu-Qiang
FQ
Kim
Hui Jung
HJ
Romberger
Debra J
DJ
Rennard
Stephen I
SI
D000818:Animals; D001249:Asthma / Q000473:pathology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism* / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D005355:Fibrosis; D005782:Gels; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000276:immunology; D008565:Membrane Proteins; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D024042:Collagen Type I; D005353:Fibronectins; D005782:Gels; D007378:Interleukins; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone