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Recently, we have reported the anti-inflammatory and reno-protective role of angiotensin-II type-2 receptor (AT2R) activation under chronic low-grade inflammatory condition in the obese Zucker rat model. However, the role of AT2R activation in preventing lipopolysaccharide (LPS)-induced early infiltration of immune cells, inflammation and AKI is not known. Mice were treated with AT2R agonist C21 (0.3 mg\/kg), with and without AT2R antagonist PD123319 (5 mg\/kg) prior to or concurrently with LPS (5 mg\/kg) challenge. Prior-treatment with C21, but not concurrent treatment, significantly prevented the LPS-induced renal infiltration of CD11b+ immune cells, increase in the levels of circulating and\/or renal chemotactic cytokines, particularly interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) and markers of renal dysfunction (blood urea nitrogen and albuminuria), while preserving anti-inflammatory interleukin-10 (IL-10) production. Moreover, C21 treatment in the absence of LPS increased renal and circulating IL-10 levels. To investigate the role of IL-10 in a cross-talk between epithelial cells and monocytes, we performed in vitro conditioned media (CM) studies in human kidney proximal tubular epithelial (HK-2) cells and macrophages (differentiated human monocytes, THP-1 cells). These studies revealed that the conditioned-media derived from the C21-treated HK-2 cells reduced LPS-induced THP-1 tumor necrosis factor-\u03b1 (TNF-\u03b1) production via IL-10 originating from HK-2 cells. Our findings suggest that prior activation of AT2R is prophylactic in preventing LPS-induced renal immune cell infiltration and dysfunction, possibly via IL-10 pathway.<\/jats:p>","DOI":"10.1042\/bsr20190429","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T13:05:50Z","timestamp":1557407150000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Prevention of lipopolysaccharide-induced CD11b+ immune cell infiltration in the kidney: role of AT2 receptors"],"prefix":"10.1042","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1674-711X","authenticated-orcid":false,"given":"Sanket","family":"Patel","sequence":"first","affiliation":[{"name":"Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Dhande","sequence":"additional","affiliation":[{"name":"Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth\u00a0Alana","family":"Gray","sequence":"additional","affiliation":[{"name":"Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quaisar","family":"Ali","sequence":"additional","affiliation":[{"name":"Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-2317","authenticated-orcid":false,"given":"Tahir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Heart and Kidney Institute, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"2021111619343988900_B1","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/S0140-6736(11)61454-2","article-title":"Acute kidney injury","volume":"380","author":"Bellomo","year":"2012","journal-title":"Lancet North Am. 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