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Despite the advances in the knowledge of the pathogenesis of systemic and local effects induced by<jats:italic>Bothrops<\/jats:italic>venom, the target tissues to this venom are not completely characterised. As preadipocytes are important cells of the adipose tissue and synthesize inflammatory mediators, we investigated the ability of<jats:italic>B<\/jats:italic>.<jats:italic>moojeni<\/jats:italic>snake venom (Bmv) to stimulate an inflammatory response in 3T3-L1 preadipocytes<jats:italic>in vitro<\/jats:italic>, focusing on (1) the release of PGE<jats:sub>2<\/jats:sub>, IL-6, TNF-\u03b1, MCP-1, KC, leptin and adiponectin; (2) the mechanisms involved in PGE<jats:sub>2<\/jats:sub>release and (3) differentiation of these cells. Cytotoxicity of Bmv was determined by MTT assay. The concentrations of PGE<jats:sub>2<\/jats:sub>, cytokines and adipokines were quantified by EIA. Participation of the COX-1 and COX-2 enzymes, NF-\u03baB and PGE<jats:sub>2<\/jats:sub>receptors (EP1-4) was assessed using a pharmacological approach, and protein expression of the COX enzymes and P-NF-\u03baB was analysed by western blotting. Preadipocyte differentiation was quantified by Oil Red O staining. Bmv (1 \u03bcg\/mL) induced release of PGE<jats:sub>2<\/jats:sub>, IL-6 and KC and increased expression of COX-2 in preadipocytes. Basal levels of TNF-\u03b1, MCP-1, leptin and adiponectin were not modified. Treatment of cells with SC560 (COX-1 inhibitor) and NS398 (COX-2 inhibitor) inhibited Bmv-induced PGE<jats:sub>2<\/jats:sub>release. Bmv induced phosphorylation of NF-\u03baB, and treatment of the cells with TPCK and SN50, which inhibit distinct NF-\u03baB domains, significantly reduced Bmv-induced PGE<jats:sub>2<\/jats:sub>release, as did the treatment with an antagonist of PGE<jats:sub>2<\/jats:sub>receptor EP1, unlike treatment with antagonists of EP2, EP3 or EP4. Bmv also induced lipid accumulation in differentiating cells. These results demonstrate that Bmv can activate an inflammatory response in preadipocytes by inducing the release of inflammatory mediators; that PGE<jats:sub>2<\/jats:sub>production is mediated by the COX-1, COX-2 and NF-\u03baB pathways; and that engagement of EP1 potentiates PGE<jats:sub>2<\/jats:sub>synthesis via a positive feedback mechanism. Our findings highlight the role of the adipose tissue as another target for Bmv and suggest that it contributes to<jats:italic>Bothrops<\/jats:italic>envenomation by producing inflammatory mediators.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010658","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T17:33:43Z","timestamp":1659980023000},"page":"e0010658","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bothrops moojeni snake venom induces an inflammatory response in preadipocytes: Insights into a new aspect of envenomation"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-8316","authenticated-orcid":true,"given":"Rodrigo","family":"Maia-Marques","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7601-5191","authenticated-orcid":true,"given":"Danilo Santos","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0557-1625","authenticated-orcid":true,"given":"Priscila Motta","family":"Janovits","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"DeOcesano-Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elbio","family":"Leiguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5887-7663","authenticated-orcid":true,"given":"Catarina","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"pntd.0010658.ref001","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40409-017-0127-6","article-title":"Snakebite envenomation turns again into a neglected tropical disease!","volume":"23","author":"J-P Chippaux","year":"2017","journal-title":"J Venom Anim Toxins Incl Trop Dis"},{"key":"pntd.0010658.ref002","doi-asserted-by":"crossref","first-page":"805","DOI":"10.4269\/ajtmh.1992.47.805","article-title":"A clinical and epidemiologic-study of 292 cases of lance-headed viper bite in a brazilian teaching hospital","volume":"47","author":"A Nishioka S de","year":"1992","journal-title":"Am Soc Trop Med Hyg"},{"key":"pntd.0010658.ref003","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1670\/120-02A","article-title":"Ecology of the Pitviper, Bothrops moojeni, in the Brazilian Cerrado","volume":"37","author":"C Nogueira","year":"2003","journal-title":"J Herpetol"},{"key":"pntd.0010658.ref004","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.tmaid.2013.03.004","article-title":"Envenomation by Bothrops atrox in a traveler to Manaus, Brazil","volume":"11","author":"S Larr\u00e9ch\u00e9","year":"2013","journal-title":"Travel Med Infect Dis"},{"key":"pntd.0010658.ref005","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cbi.2017.12.022","article-title":"Evaluation of pro-inflammatory events induced by Bothrops alternatus snake venom","volume":"281","author":"S Echeverr\u00eda","year":"2018","journal-title":"Chem Biol Interact"},{"key":"pntd.0010658.ref006","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1177\/1535370215590818","article-title":"Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis","volume":"240","author":"V. 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