Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages

Citation
Mr. Horton et al., Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages, J IMMUNOL, 162(7), 1999, pp. 4171-4176
Citations number
53
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
162
Issue
7
Year of publication
1999
Pages
4171 - 4176
Database
ISI
SICI code
0022-1767(19990401)162:7<4171:IAROMM>2.0.ZU;2-3
Abstract
Although the metalloproteinase murine metalloelastase (MME) has been implic ated in lung disorders such as emphysema and pulmonary fibrosis, the mechan isms regulating MME expression are unclear. Low m.w. fragments of the extra cellular matrix component hyaluronan (HA) that accumulate at sites of lung inflammation are capable of inducing inflammatory gene expression in macrop hages (M phi). The purpose of this study was to examine the effect of HA fr agments on the expression of MIME in alveolar M phi. The mouse alveolar M p hi cell line MH-S was stimulated with HA fragments over time, total RNA was isolated, and Northern blot analysis was performed. HA fragments induced M ME mRNA in a time-dependent fashion, with maximal levels at 6 h, HA fragmen ts also induced MME protein expression as well as enzyme activity. The indu ction of MME gene expression was specific for low m.w. HA fragments and dep endent upon new protein synthesis; it occurred at the level of gene transcr iption. We also examined the effect of HA fragments on MME expression in in flammatory alveolar M phi from bleomycin-injured rat lungs, Although normal rat alveolar M phi did not express MME mRNA in response to HA fragments, a lveolar M phi from the bleomycin-treated rats responded to HA fragment stim ulation by increasing MME mRNA levels. Furthermore, baseline and HA fragmen t-induced MIME gene expression in alveolar M phi from bleomycin-treated rat s was inhibited by IPN-gamma. These data suggest that HA fragments may be a n important mechanism for the expression of MME by M phi in inflammatory lu ng disorders.