Mediation of macrophage collagenase production by 3'-5' cyclic adenosine monophosphate

J. B. McCarthy, S. M. Wahl, J. C. Rees, C. E. Olsen, L. Sandberg, L. M. Wahl

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The production of collagenase by lipopolysaccharide-(LPS) activated guinea pig macrophages is mediated by prostaglandins (PG) of the E series. After stimulation of guinea pig macrophages with LPS, extracellular PGE levels and cellular cAMP levels are elevated. Indomethacin inhibits not only PG synthesis, but also cAMP and collagenase production in LPS-stimulated macrophage cultures. In these indomethacin-inhibited cultures containing LPS, dibutyryl (dB) cAMP, or cholera toxin can restore macrophage collagenase production but not PG synthesis. Moreover, dBcAMP and cholera toxin enhance collagenase production in LPS-activated cultures. Initial activation of the macrophages by an agent such as LPS is a prerequisite for synthesis of collagenase, since in the absence of LPS, dBcAMP or cholera toxin alone are ineffective stimuli. These findings clearly demonstrate a role for PG-induced elevations of cAMP in the production of collagenase by LPS-activated macrophages.

Original languageEnglish (US)
Pages (from-to)2405-2409
Number of pages5
JournalJournal of Immunology
Volume124
Issue number5
StatePublished - Jul 18 1980

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