Open AccessCoordinate expression of group II phospholipase A 2 and the acute‐phase proteins haptoglobin (HP) and α 1 ‐anti‐chymotrypsin (ACH) by HepG2 cells
Author(s) -
VADAS P.,
GROUIX B.,
STEFANSKI E.,
WLOCH M.,
PRUZANSKI W.,
SCHROEDER J.,
GAULDIE J.
Publication year - 1997
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1997.d01-990.x
Subject(s) - haptoglobin , acute phase protein , phospholipase a2 , chymotrypsin , immunology , phospholipase a , biology , chemistry , enzyme , biochemistry , trypsin , inflammation
The early response to inflammation is characterized by the synthesis of a variety of proteins under cytokine and glucocorticoid control. During episodes of infection or inflammation, a secretory phospholipase A 2 (sPLA 2 ) appears in the circulation along with a variety of acute‐phase proteins (APP), suggesting possible common regulatory elements amongst sPLA 2 and APP. Using the human hepatoma line, HepG2, regulation of sPLA 2 expression was examined in relation to synthesis of HP and ACH. The patterns of induction of sPLA 2 , HP and ACH were distinct for each of IL‐1, tumour necrosis factor (TNF) and IL‐6, oncostatin M, IL‐11 and leukaemia inhibitory factor. Dexamethasone had an enhancing effect on IL‐6‐induced expression of HP and ACH, but inhibited sPLA 2 expression by 50%. Both 8‐bromo‐cAMP and dibutyryl cAMP increased sPLA 2 expression (48.8‐fold and 64.2‐fold, respectively), whereas KT5720, an inhibitor of protein kinase A, down‐regulated cytokine‐induced sPLA 2 synthesis by 51%. These data show that a panel of cytokines induced varying patterns of up‐regulation of sPLA 2 , ACH and HP. Although dexamethasone potentiated IL‐6‐induced APP expression in HepG2 cells, it suppressed sPLA 2 expression in a dose‐dependent manner. In several respects, sPLA 2 regulation is similar to that of HP and ACH, but a notable difference is the reciprocal effect of glucocorticoids on sPLA 2 expression compared with that of ACH and HP.