PMID- 25888869 OWN - NLM STAT- MEDLINE DCOM- 20160307 LR - 20181113 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 12 DP - 2015 Feb 27 TI - MCP-induced protein 1 mediates the minocycline-induced neuroprotection against cerebral ischemia/reperfusion injury in vitro and in vivo. PG - 39 LID - 10.1186/s12974-015-0264-1 [doi] LID - 39 AB - BACKGROUND: Minocycline, a broad-spectrum tetracycline antibiotic, has shown anti-inflammatory and neuroprotective effects in ischemic brain injury. The present study seeks to determine whether monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified modulator of inflammatory reactions, is involved in the cerebral neuroprotection conferred by minocycline treatment in the animal model of focal cerebral ischemia and to elucidate the mechanisms of minocycline-induced ischemic brain tolerance. METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h in male C57BL/6 mice and MCPIP1 knockout mice followed by 24- or 48-h reperfusion. Twelve hours before ischemia or 2 h after MCAO, mice were injected intraperitoneally with 90 mg/kg of minocycline hydrochloride. Thereafter, the animals were injected twice a day, at a dose of 90 mg/kg after ischemia until sacrificed. Transcription and expression of MCPIP1 gene was monitored by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. The neurobehavioral scores, infarction volumes, and proinflammatory cytokines in brain and NF-kappaB signaling were evaluated after ischemia/reperfusion. RESULTS: MCPIP1 protein and mRNA levels significantly increased in mouse brain undergoing minocycline pretreatment. Minocycline treatment significantly attenuated the infarct volume, neurological deficits, and upregulation of proinflammatory cytokines in the brain of wild type mice after MCAO. MCPIP1-deficient mice failed to evoke minocycline-treatment-induced tolerance compared with that of the control MCPIP1-deficient group without minocycline treatment. Similarly, in vitro data showed that minocycline significantly induced the expression of MCPIP1 in primary neuron-glial cells, cortical neurons, and reduced oxygen glucose deprivation (OGD)-induced cell death. The absence of MCPIP1 blocked minocycline-induced protection on neuron-glial cells and cortical neurons treated with OGD. CONCLUSIONS: Our in vitro and in vivo studies demonstrate that MCPIP1 is an important mediator of minocycline-induced protection from brain ischemia. FAU - Jin, Zhuqing AU - Jin Z AD - School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China. jinzq@hotmail.com. FAU - Liang, Jian AU - Liang J AD - Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, 4000 Central Florida Boulevard, Orlando, FL, 32816, USA. jian.liang@ucf.edu. FAU - Wang, Jing AU - Wang J AD - Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, 4000 Central Florida Boulevard, Orlando, FL, 32816, USA. jwang7882@gmail.com. FAU - Kolattukudy, Pappachan E AU - Kolattukudy PE AD - Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, 4000 Central Florida Boulevard, Orlando, FL, 32816, USA. pappachan.kolattukudy@ucf.edu. LA - eng GR - R01 HL069458/HL/NHLBI NIH HHS/United States GR - R56 HL069458/HL/NHLBI NIH HHS/United States GR - HL69458/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150227 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Cytokines) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Neuroprotective Agents) RN - EC 3.1.- (Ribonucleases) RN - EC 3.1.- (Zc3h12a protein, mouse) RN - EC 4.2.1.11 (Phosphopyruvate Hydratase) RN - FYY3R43WGO (Minocycline) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Brain Edema/etiology MH - Brain Infarction/diagnosis/etiology MH - Cells, Cultured MH - Cytokines/genetics/metabolism MH - Disease Models, Animal MH - Gene Expression Regulation/drug effects/genetics MH - Glial Fibrillary Acidic Protein/metabolism MH - Glucose/deficiency MH - Hypoxia/prevention & control MH - Infarction, Middle Cerebral Artery/*complications MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Minocycline/*therapeutic use MH - Neurologic Examination MH - Neurons/drug effects MH - Neuroprotective Agents/*therapeutic use MH - Phosphopyruvate Hydratase/metabolism MH - Reperfusion Injury/*etiology/*prevention & control MH - Ribonucleases/genetics/*metabolism MH - Time Factors PMC - PMC4359584 EDAT- 2015/04/19 06:00 MHDA- 2016/03/08 06:00 PMCR- 2015/02/27 CRDT- 2015/04/19 06:00 PHST- 2014/08/31 00:00 [received] PHST- 2015/02/10 00:00 [accepted] PHST- 2015/04/19 06:00 [entrez] PHST- 2015/04/19 06:00 [pubmed] PHST- 2016/03/08 06:00 [medline] PHST- 2015/02/27 00:00 [pmc-release] AID - 10.1186/s12974-015-0264-1 [pii] AID - 264 [pii] AID - 10.1186/s12974-015-0264-1 [doi] PST - epublish SO - J Neuroinflammation. 2015 Feb 27;12:39. doi: 10.1186/s12974-015-0264-1.