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Lipoxin A 4 and aspirin‐triggered 15‐epi‐LXA 4 inhibit tumor necrosis factor‐α‐initiated neutrophil responses and trafficking: novel regulators of a cytokine—chemokine axis relevant to periodontal diseases
Author(s) -
Pouliot Marc,
Serhan Charles N.
Publication year - 1999
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.1999.tb02268.x
Subject(s) - chemokine , tumor necrosis factor alpha , cytokine , chemistry , immunology , microbiology and biotechnology , cancer research , medicine , inflammation , biology
The impact of lipoxin A 4 (LXA 4 ) and aspirin‐triggered‐lipoxins (ATL) was investigated in tumor necrosis factor (TNFα)‐initiated neutrophil (PMN) responses in vitro and in vivo using LX analogs that are metabolically more stable. At nanoraolar levels, the LXA 4 and ATL analog 15 R/S‐methyl‐LXA 4 each blocked TNFa‐stimulated IL‐1β release by isolated human PMN in vitro . These LXA 4 ‐ATL actions were time‐ and concentration‐dependent. The TNFα‐induced IL‐1β gene expression was also regulated by 15 R/S‐methyl‐LXA 4 . In addition, 15 R/S‐methyl‐LXA 4 added to murine air pouches dramatically inhibited TNFα‐stimulated leukocyte trafficking in vivo , as well as altered the appearance of both macrophage inflammatory peptide‐2 and IL‐1 ji and concomitantly stimulated IL‐4 in pouch exudates. These findings from in vitro and in vivo experiments indicate that both LXA 4 and ATL are regulators of TNFα‐directed neutrophil actions and stimulate IL‐4 in exudates and thus regulate mediators that are held to play an important role in the pathogenesis of periodontal disease.