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The constitutively-expressed cyclooxygenase 1(COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid(AA) to prostaglandins(PGs).However,the functional roles of COX-1 at the cellular level remain unclear.We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type(WT) mice and COX-2~(-/-) or COX-1~(-/-) mice may help address the functional roles of COX-1 in inflammation and other cellular functions.Compared to WT,the number of specifically-induced transcripts were altered descendingly as follows:COX-2~(-/-) > COX-1~(-/-) > WT + IL-1β.COX-1~(-/-) or COX-2~(-/-) cells shared about 50%of the induced transcripts with WT cells treated with IL-1β,respectively.An interactive “anti-inflammatory,proinflammatory,and redox-activated” signature in the protein-protein interactome map was observed in COX-2~(-/-) cells.The augmented COX-1mRNA(in COX-2~(-/-) cells) was associated with the upregulation of mRNAs for glutathione S-transferase(GST),superoxide dismutase(SOD),NAD(P)H dehydrogenase quinone 1(NQO1),aryl hydrocarbon receptor(AhR),peroxiredoxin,phospholipase,prostacyclin synthase,and prostaglandin E synthase,resulting in a significant increase in the levels of PGE_2,PGD_2,leukotriene B_4(LTB_4),PGF_(1α),thromboxane B_2(TXB_2),and PGF_(2α).The COX-1 plays a dominant role in shifting AA toward the LTB_4 pathway and anti-inflammatory activities.Compared to WT,the upregulated COX-1 mRNA in COX-2~(-/-) cells generated an “eicosanoid storm”.The genomic characteristics of COX-2~(-/-) is similar to that of proinflammatory cells as observed in IL-1β induced WT cells.COX-1~(-/-) and COX-2~(-/-) cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.
The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear .We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2 ~ (- / -) or COX-1 ~ (- / -) mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered ascending: COX-2 ~ (- / -)> COX- IL-1β.COX-1 ~ (- / -) or COX-2 ~ (- / -) cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive “anti-inflammatory , proinflammatory, and redox-activated ”signature in the protein-protein interactome map was observed in COX-2 ~ (- / -) cells. associated with the upregulation of mRNAs for glutathione S-transferase (GST), superoxide dismutase (SOD), NAD (P) H dehydrogenase quinone 1 (NQO1), aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE_2, PGD_2, leukotriene B_4 (LTB_4), PGF_ (1α), thromboxane B_2 (TXB_2), and PGF_ (2α) .The COX-1 plays a dominant role in shifting AA toward the LTB_4 pathway and anti -inflammatory activities .Compared to WT, the upregulated COX-1 mRNA in COX-2 ~ (- / -) cells generated an “eicosanoid storm”. The genomic characteristics of COX-2 ~ (- / -) are similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1 ~ (- / -) and COX-2 ~ (- / -) cells display compensation of various eicosanoids at the genomic and metabolic levels.