TY - JOUR
T1 - Hyaluronan fragments induce nitric-oxide synthase in murine macrophages through a nuclear factor κB-dependent mechanism
AU - McKee, Charlotte M.
AU - Lowenstein, Charles J.
AU - Horton, Maureen R.
AU - Wu, Jean
AU - Bao, Clare
AU - Chin, Beek Yoke
AU - Choi, Augustine M.K.
AU - Noble, Paul W.
PY - 1997
Y1 - 1997
N2 - Activated macrophages play a critical role in controlling chronic tissue inflammation through the release of a variety of mediators including cytokines, chemokines, growth factors, active lipids, reactive oxygen, and nitrogen species. The mechanisms that regulate macrophage activation in chronic inflammation are poorly understood. A hallmark of chronic inflammation is the turnover of extracellular matrix components, and recent work has suggested that interactions with the extracellular matrix can exert important influences on macrophage effector functions. We have examined the effect of low molecular weight fragments of the extracellular matrix glycosaminoglycan hyaluronan (HA) on the induction of nitric-oxide synthase (iNOS) in macrophages. We found that HA fragments induce iNOS mRNA, protein and activity alone, and markedly synergize with interferon-γ to induce iNOS gene expression in murine macrophages. In addition, we found that resident tissue alveolar macrophages respond minimally, but inflammatory alveolar macrophages exhibit a marked induction in iNOS expression in response to HA fragments. Finally, we demonstrate that the mechanism of HA fragment-induced expression of iNOS requires activation of the transcriptional regulator nuclear factor KB. These data support the hypothesis that HA may be an important regulator of macrophage activation at sites of chronic tissue inflammation.
AB - Activated macrophages play a critical role in controlling chronic tissue inflammation through the release of a variety of mediators including cytokines, chemokines, growth factors, active lipids, reactive oxygen, and nitrogen species. The mechanisms that regulate macrophage activation in chronic inflammation are poorly understood. A hallmark of chronic inflammation is the turnover of extracellular matrix components, and recent work has suggested that interactions with the extracellular matrix can exert important influences on macrophage effector functions. We have examined the effect of low molecular weight fragments of the extracellular matrix glycosaminoglycan hyaluronan (HA) on the induction of nitric-oxide synthase (iNOS) in macrophages. We found that HA fragments induce iNOS mRNA, protein and activity alone, and markedly synergize with interferon-γ to induce iNOS gene expression in murine macrophages. In addition, we found that resident tissue alveolar macrophages respond minimally, but inflammatory alveolar macrophages exhibit a marked induction in iNOS expression in response to HA fragments. Finally, we demonstrate that the mechanism of HA fragment-induced expression of iNOS requires activation of the transcriptional regulator nuclear factor KB. These data support the hypothesis that HA may be an important regulator of macrophage activation at sites of chronic tissue inflammation.
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U2 - 10.1074/jbc.272.12.8013
DO - 10.1074/jbc.272.12.8013
M3 - Article
C2 - 9065473
AN - SCOPUS:0030944222
VL - 272
SP - 8013
EP - 8018
JO - The Journal of biological chemistry
JF - The Journal of biological chemistry
SN - 0021-9258
IS - 12
ER -