Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gram-negative bacterial endotoxin lipopolysaccharide (LPS) triggers the production of inflammatory cytokines, reactive oxygen species (ROS), and prostaglandins (PGs) by pulmonary macrophages. Here, we investigated if ROS influenced PGs production in response to LPS treatment in mouse bone marrow-derived macrophages (BMDM). We observed that pretreatment of BMDM with two structurally unrelated ROS scavengers, MnTMPyP and EUK-134, not only prevented LPS-induced ROS accumulation, but also attenuated the LPS-induced PGD(2), but not PGE(2), production. Conversely LPS-induced PGD(2), but not PGE(2), production, was potentiated with the cotreatment of BMDM with H(2)O(2). These data suggest that ROS differentially regulate PGD(2) and PGE(2) production in BMDM. In addition, selective inhibition of the ROS generator NADPH oxidase (NOX) using either pharmacologic inhibitors or its p47(phox) subunit deficient mouse BMDM also attenuated LPS-induced PGD(2), but not PGE(2) production, suggesting the critical role of NOX-generated ROS in LPS-induced PGD(2) production in BMDM. We further found that both hematopoietic PGD synthase (H-PGDS) siRNA and its inhibitor HQL-79, but not lipocalin PGDS (L-PGDS) siRNA and its inhibitor AT-56, significantly attenuated LPS-induced PGD(2) production, suggesting that H-PGDS, but not L-PGDS, mediates LPS-induced PGD(2) production in BMDM. Furthermore, data from our in vitro cell-free enzymatic studies showed that coincubation of the recombinant H-PGDS with either MnTMPyP, EUK-134, or catalase significantly decreased PGD(2) production, whereas coincubation with H(2)O(2) significantly increased PGD(2) production. Taken together, our results show that LPS-induced NOX-generated ROS production differentially and specifically regulates the H-PGDS-mediated production of PGD(2), but not PGE(2), in mouse BMDM.
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PMID:Pivotal role of reactive oxygen species in differential regulation of lipopolysaccharide-induced prostaglandins production in macrophages. 2307 Nov 5