PMID- 31666088 OWN - NLM STAT- MEDLINE DCOM- 20200330 LR - 20201114 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 16 IP - 1 DP - 2019 Oct 30 TI - CD147 as a key mediator of the spleen inflammatory response in mice after focal cerebral ischemia. PG - 198 LID - 10.1186/s12974-019-1609-y [doi] LID - 198 AB - BACKGROUND: The splenic inflammatory response after cerebral ischemia has been implicated in secondary brain injury. We have recently reported that CD147 plays an important role in driving brain inflammation after ischemic stroke. In this study, we hypothesized that CD147 may play a role in the splenic inflammatory response after cerebral ischemia. METHODS: Transient (60 min) middle cerebral artery occlusion was induced in wild-type mice treated with an anti-CD147 antibody (alphaCD147) 1 h before ischemia onset. The splenic inflammatory response was evaluated at 4 and 24 h, representing the peak and early stage of splenic inflammatory activation in this model. Changes in mRNA and protein expression of CD147 and inflammatory markers were measured using RT-qPCR and western blot, respectively. Immune cells in the spleen and brain were measured using flow cytometry. RESULTS: CD147 expression was rapidly upregulated in the spleen at 4 and 24 h after ischemia onset. The splenic inflammatory response induced by cerebral ischemia was inhibited by alphaCD147 treatment as demonstrated by the reduced expression of cytokines (TNFalpha, IL-6, IL-1beta) and monocyte chemoattractant protein-1 (MCP-1) in the spleen at 4 and 24 h after ischemia onset. Furthermore, reduced expression of Ly-6C and CCR2 coincided with a decrease in the number of Ly-6C(high) MMs subset in the spleen at 4 h after ischemia onset. This suggests alphaCD147 treatment abrogates cerebral ischemia-induced inflammatory activation of splenic monocytes/macrophages (MMs). In addition, the experiment in splenectomized mice showed the spleen as the major source of infiltrated Ly-6C(high) MMs subset in the ischemic brain and that brain infiltration of Ly-6C(high) MMs was reduced by alphaCD147 treatment. These results reveal CD147 as a key mediator of the spleen's inflammatory activation in response to cerebral ischemia. FAU - Jin, Rong AU - Jin R AD - Department of Neurosurgery, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA. FAU - Zhong, Wei AU - Zhong W AD - Department of Neurosurgery, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA. AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Jiefang road 438, Zhenjiang, 212013, Jiangsu Province, China. FAU - Liu, Shan AU - Liu S AD - Department of Neurosurgery, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA. FAU - Li, Guohong AU - Li G AD - Department of Neurosurgery, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA. guohongli@pennstatehealth.psu.edu. LA - eng GR - R01 NS088719/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20191030 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Antibodies, Monoclonal) RN - 0 (Bsg protein, mouse) RN - 136894-56-9 (Basigin) SB - IM MH - Animals MH - Antibodies, Monoclonal/pharmacology/therapeutic use MH - Basigin/*antagonists & inhibitors/*physiology MH - Brain Ischemia/drug therapy/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Spleen/drug effects/*metabolism/pathology MH - Stroke/drug therapy/*metabolism PMC - PMC6822438 OTO - NOTNLM OT - CD147 OT - Cerebral ischemia OT - Cytokines OT - Inflammation OT - Monocytes/macrophages OT - Spleen COIS- The authors declare that they have no competing interests. EDAT- 2019/11/02 06:00 MHDA- 2020/03/31 06:00 PMCR- 2019/10/30 CRDT- 2019/11/01 06:00 PHST- 2019/04/03 00:00 [received] PHST- 2019/10/01 00:00 [accepted] PHST- 2019/11/01 06:00 [entrez] PHST- 2019/11/02 06:00 [pubmed] PHST- 2020/03/31 06:00 [medline] PHST- 2019/10/30 00:00 [pmc-release] AID - 10.1186/s12974-019-1609-y [pii] AID - 1609 [pii] AID - 10.1186/s12974-019-1609-y [doi] PST - epublish SO - J Neuroinflammation. 2019 Oct 30;16(1):198. doi: 10.1186/s12974-019-1609-y.