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10.1111/bph.13210

http://scihub22266oqcxt.onion/10.1111/bph.13210
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C4556470!4556470!26040494
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suck abstract from ncbi


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pmid26040494      Br+J+Pharmacol 2015 ; 172 (17): 4319-30
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  • 15-Lipoxygenases regulate the production of chemokines in human lung macrophages #MMPMID26040494
  • Abrial C; Grassin-Delyle S; Salvator H; Brollo M; Naline E; Devillier P
  • Br J Pharmacol 2015[Sep]; 172 (17): 4319-30 PMID26040494show ga
  • Background and Purpose: 15-Lipoxygenase (15-LOX) activity is associated with inflammation and immune regulation. The objectives of the present study were to investigate the expression of 15-LOX-1 and 15-LOX-2 and evaluate the enzymes? roles in the polarization of human lung macrophages (LMs) in response to LPS and Th2 cytokines (IL-4/-13). Experimental Approach: LMs were isolated from patients undergoing surgery for carcinoma. The cells were cultured with a 15-LOX inhibitor (PD146176 or ML351), a COX inhibitor (indomethacin), a 5-LOX inhibitor (MK886) or vehicle and then stimulated with LPS (10?ng·mL?1), IL-4 (10?ng·mL?1) or IL-13 (50?ng·mL?1) for 24?h. Levels of ALOX15 (15-LOX-1) and ALOX15B (15-LOX-2) transcripts were determined by real-time quantitative PCR. Immunoassays were used to measure levels of LPS-induced cytokines (TNF-?, CCL2, CCL3, CCL4, CXCL1, CXCL8 and CXCL10) and Th2 cytokine-induced chemokines (CCL13, CCL18 and CCL22) in the culture supernatant. Key Results: Stimulation of LMs with LPS was associated with increased expression of ALOX15B, whereas stimulation with IL-4/IL-13 induced the expression of ALOX15. PD146176 and ML351 (10??M) reduced the release of the chemokines induced by LPS and Th2 cytokines. The effects of these 15-LOX inhibitors were maintained in the presence of indomethacin and MK886. Furthermore, indomethacin revealed the inhibitory effect of PD146176 on TNF-? release. Conclusions and Implications: Inhibition of the 15-LOX pathways is involved in the down-regulation of the in vitro production of chemokines in LMs. Our results suggest that the 15-LOX pathways have a role in the pathogenesis of inflammatory lung disorders and may thus constitute a potential drug target.
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