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Critical Role of TLR 2 and MyD 88 for Functional Response of Macrophages to a Group IIA-Secreted Phospholipase A 2 from Snake Venom
| Content Provider | Semantic Scholar |
|---|---|
| Author | Leiguez, Elbio Giannotti, Karina Cristina Moreira, Vanessa Matsubara, Márcio Hideki José Gutiérrez, María Teresa Urdiales Lomonte, Bruno Rodríguez, Juan P. Balsinde, Jesús Teixeira, Catarina |
| Copyright Year | 2014 |
| Abstract | The snake venom MT-III is a group IIA secreted phospholipase A2 (sPLA2) enzyme with functional and structural similarities with mammalian pro-inflammatory sPLA2s of the same group. Previously, we demonstrated that MT-III directly activates the innate inflammatory response of macrophages, including release of inflammatory mediators and formation of lipid droplets (LDs). However, the mechanisms coordinating these processes remain unclear. In the present study, by using TLR2 or MyD88 or C57BL/6 (WT) male mice, we report that TLR2 and MyD88 signaling have a critical role in MT-III-induced inflammatory response in macrophages. MT-III caused a marked release of PGE2, PGD2, PGJ2, IL-1b and IL-10 and increased the number of LDs in WT macrophages. In MT-III-stimulated TLR2 macrophages, formation of LDs and release of eicosanoids and cytokines were abrogated. In MyD88 macrophages, MT-III-induced release of PGE2, IL-1b and IL-10 was abrogated, but release of PGD2 and PGJ2 was maintained. In addition, COX-2 protein expression seen in MT-III-stimulated WT macrophages was abolished in both TLR2 and MyD88 cells, while perilipin 2 expression was abolished only in MyD88 cells. We further demonstrated a reduction of saturated, monounsaturated and polyunsaturated fatty acids and a release of the TLR2 agonists palmitic and oleic acid from MT-III-stimulated WT macrophages compared with WT control cells, thus suggesting these fatty acids as major messengers for MT-III-induced engagement of TLR2/MyD88 signaling. Collectively, our findings identify for the first time a TLR2 and MyD88-dependent mechanism that underlies group IIA sPLA2induced inflammatory response in macrophages. Citation: Leiguez E, Giannotti KC, Moreira V, Matsubara MH, Gutiérrez JM, et al. (2014) Critical Role of TLR2 and MyD88 for Functional Response of Macrophages to a Group IIA-Secreted Phospholipase A2 from Snake Venom. PLoS ONE 9(4): e93741. doi:10.1371/journal.pone.0093741 Editor: Patricia T. Bozza, Fundação Oswaldo Cruz, Brazil Received November 21, 2013; Accepted March 6, 2014; Published April 9, 2014 Copyright: 2014 Leiguez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This investigation was supported by research grants from FAPESP, São Paulo, Brazil (www.fapesp.br), grants 11/21341-5 and 10/06345-1, INCTTOX, São Paulo, Brazil (www.incttox.com.br), grant 573790/2008-6, CNPq PQ, Brazil (www.cnpq.br), grant 306920/2011-5, Brazil, Spanish Ministery of Science and Innovation, Spain (http://web.micinn.es/), grant BFU2010-18826. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: cteixeir@usp.br |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.kerwa.ucr.ac.cr/bitstream/handle/10669/11084/2014_PLA2_PLoSOne_Leiguez_Mt-III_TLR2_macrophages.pdf?isAllowed=y&sequence=1 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
