PMID- 33248911 OWN - NLM STAT- MEDLINE DCOM- 20220118 LR - 20220118 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 138 DP - 2021 Feb TI - Macrophage-polarizing stimuli differentially modulate the inflammatory profile induced by the secreted phospholipase A(2) group IA in human lung macrophages. PG - 155378 LID - S1043-4666(20)30394-X [pii] LID - 10.1016/j.cyto.2020.155378 [doi] AB - In this study we investigated the effects of snake venom Group IA secreted phospholipase A(2) (svGIA) on the release of inflammatory and angiogenic mediators from human lung macrophages (HLMs). HLMs were incubated with lipopolysaccharide (LPS) or svGIA with or without macrophage-polarizing stimuli (IL-4, IL-10, IFN-gamma or the adenosine analogue NECA). M2-polarizing cytokines (IL-4 and IL-10) inhibited TNF-alpha, IL-6, IL-12, IL-1beta, CXCL8 and CCL1 release induced by both LPS and svGIA. IL-4 inhibited also the release of IL-10. IFN-gamma reduced IL-10 and IL-12 and increased CCL1 release by both the LPS and svGIA-stimulated HLMs, conversely IFN-gamma reduced IL-1beta only by svGIA-stimulated HLMs. In addition, IFNgamma promoted TNF-alpha and IL-6 release from svGIA-stimulated HLMs to a greater extent than LPS. NECA inhibited TNF-alpha and IL-12 but promoted IL-10 release from LPS-stimulated HLMs according to the well-known effect of adenosine in down-regulating M1 activation. By contrast NECA reduced TNF-alpha, IL-10, CCL1 and IL-1beta release from svGIA-activated HLM. IL-10 and NECA increased both LPS- and svGIA-induced vascular endothelial growth factor A (VEGF-A) release. By contrast, IL-10 reduced angiopoietin-1 (ANGPT1) production from activated HLMs. IFN-gamma and IL-4 reduced VEGF-A and ANGPT1 release from both LPS- and svGIA-activated HLMs. Moreover, IL-10 inhibited LPS-induced ANGPT2 production. In conclusion, we demonstrated a fine-tuning modulation of svGIA-activated HLMs differentially exerted by the classical macrophage-polarizing cytokines. CI - Copyright (c) 2020. Published by Elsevier Ltd. FAU - Ferrara, Anne Lise AU - Ferrara AL AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy; Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council, Naples, Italy. Electronic address: anneliseferrara@gmail.com. FAU - Galdiero, Maria Rosaria AU - Galdiero MR AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy; Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council, Naples, Italy. Electronic address: mariarosaria.galdiero@unina.it. FAU - Fiorelli, Alfonso AU - Fiorelli A AD - Translational Medical and Surgical Science, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: alfonso.fiorelli@unicampania.it. FAU - Cristinziano, Leonardo AU - Cristinziano L AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy. Electronic address: l.cristinziano@gmail.com. FAU - Granata, Francescopaolo AU - Granata F AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy. Electronic address: frapagra@hotmail.com. FAU - Marone, Giancarlo AU - Marone G AD - Department of Public Health, University of Naples Federico II, Italy; Monaldi Hospital Pharmacy, Naples, Italy. Electronic address: gcmarone@hotmail.it. FAU - Crescenzo, Rosa Maria Di AU - Crescenzo RMD AD - Translational Medical and Surgical Science, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: rosa.dicrescenzo@unina.it. FAU - Braile, Mariantonia AU - Braile M AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy. Electronic address: brailemariantonia@gmail.com. FAU - Marcella, Simone AU - Marcella S AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy. Electronic address: s.marcella92@gmail.com. FAU - Modestino, Luca AU - Modestino L AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy. Electronic address: modestino.luca@gmail.com. FAU - Varricchi, Gilda AU - Varricchi G AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy; Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council, Naples, Italy. Electronic address: gildanet@gmail.com. FAU - Spadaro, Giuseppe AU - Spadaro G AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy. Electronic address: giuseppe.spadaro@unina.it. FAU - Santini, Mario AU - Santini M AD - Translational Medical and Surgical Science, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: mario.santini@unicampania.it. FAU - Loffredo, Stefania AU - Loffredo S AD - Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples "Federico II", Naples, Italy; WAO Center of Excellence, Naples, Italy; Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Research Council, Naples, Italy. Electronic address: stefanialoffredo@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201125 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (ANGPT1 protein, human) RN - 0 (Angiopoietin-1) RN - 0 (CCL1 protein, human) RN - 0 (CXCL8 protein, human) RN - 0 (Chemokine CCL1) RN - 0 (Cytokines) RN - 0 (IL10 protein, human) RN - 0 (IL4 protein, human) RN - 0 (Interleukin-8) RN - 0 (Lipopolysaccharides) RN - 0 (TNF protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - EC 3.1.1.4 (Group IB Phospholipases A2) SB - IM MH - Angiopoietin-1/metabolism MH - Animals MH - Cell Differentiation MH - Chemokine CCL1/metabolism MH - Cytokines/metabolism MH - Group IB Phospholipases A2/*metabolism MH - Humans MH - Inflammation MH - Interleukin-10/metabolism MH - Interleukin-4/metabolism MH - Interleukin-8/metabolism MH - Lipopolysaccharides/pharmacology MH - Lung/*metabolism MH - Macrophage Activation/drug effects MH - Macrophages/*metabolism MH - Macrophages, Alveolar/metabolism MH - Monocytes/cytology MH - Neovascularization, Pathologic MH - Snakes MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Angiogenesis OT - Inflammation OT - Macrophage polarization OT - Secretory phospholipases A(2) EDAT- 2020/11/30 06:00 MHDA- 2022/01/19 06:00 CRDT- 2020/11/29 20:27 PHST- 2020/04/27 00:00 [received] PHST- 2020/10/12 00:00 [revised] PHST- 2020/11/18 00:00 [accepted] PHST- 2020/11/30 06:00 [pubmed] PHST- 2022/01/19 06:00 [medline] PHST- 2020/11/29 20:27 [entrez] AID - S1043-4666(20)30394-X [pii] AID - 10.1016/j.cyto.2020.155378 [doi] PST - ppublish SO - Cytokine. 2021 Feb;138:155378. doi: 10.1016/j.cyto.2020.155378. Epub 2020 Nov 25.