Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1988-9-9
pubmed:abstractText
Arachidonate metabolites are potent biological mediators affecting multiple cellular functions. Although prostaglandins of the E series, which are products of the cyclooxygenase pathway, have been known as inhibitors or down-regulators of fibroblast proliferation and collagen synthesis, the more recently discovered products of the 5-lipoxygenase pathway have not been as extensively investigated with regard to fibroblast function. In this study, a sulfidopeptide product of the lipoxygenase pathway, leukotriene C4 (LTC4), was examined for its ability to modulate rat lung fibroblast collagen synthesis and proliferation in vitro. The data revealed the ability of LTC4 and to a lesser extent leukotriene D4 (LTD4) to stimulate collagen synthesis in a dose-dependent (10(-11)-10(-8) M) manner without affecting cellular proliferation as determined by radiolabeled thymidine incorporation; 1 nM LTC4 caused an 85% (p less than 0.02) increase above untreated controls in [3H]proline incorporation into collagenous protein in the media, which was blocked by the putative leukotriene receptor antagonist FPL55712 (10 microM) and inhibited by cycloheximide and actinomycin D. This LTC4 stimulatory effect was slightly more specific for collagen synthesis vs noncollagenous protein synthesis but was not accompanied with any change in the collagen type composition. Binding of [3H]LTC4 to these cells was specific, reversible, and saturable, with a Kd of 1.8 +/- 0.95 nM. Under equilibrium conditions, there was an estimated 2.39 X 10(4) receptors per cell. This binding was also inhibited by 10 microM FPL55712. Competitive binding studies show specificity of this binding for LTC4 relative to LTD4 and FPL55712. Furthermore, no significant conversion of LTC4 to LTD4 or leukotriene E4 was noted during the binding studies.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2846-53
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Binding of leukotriene C4 to rat lung fibroblasts and stimulation of collagen synthesis in vitro.
pubmed:affiliation
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't