Upregulation of CCL3/MIP‑1alpha regulated by MAPKs and NF‑kappaB mediates microglial inflammatory response in LPS‑induced brain injury

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Acta Neurobiologiae Experimentalis

Nencki Institute of Experimental Biology

Polish Neuroscience Society

Subject: Behavioral Sciences , Biomedical Sciences & Nutrition , Life Sciences , Medicine , Neurosciences

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ISSN: 0065-1400
eISSN: 1689-0035

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VOLUME 76 , ISSUE 4 (December 2016) > List of articles

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Upregulation of CCL3/MIP‑1alpha regulated by MAPKs and NF‑kappaB mediates microglial inflammatory response in LPS‑induced brain injury

Xiaobo Zhu / Dee Wei / Ou Chen / Zhaohua Zhang / Jiang Xue / Shanying Huang / Weiwei Zhu / Yibiao Wang *

Keywords : chemokine , MIP‑1alpha , MAPK , microglia , brain injury , rat

Citation Information : Acta Neurobiologiae Experimentalis. VOLUME 76 , ISSUE 4 , Pages 304-317 , ISSN (Online) 1689-0035, DOI: 10.21307/ane-2017-029, December 2016

License : (CC BY 4.0)

ARTICLE

ABSTRACT

Growing evidence suggests that macrophage inflammatory protein (MIP)‑1alpha (synonym CCL3) is upregulated in the neuroinflammatory processes initiated by some brain disorders, but its precise role and regulatory mechanism remain unclear. The present work aims to evaluate the role of CCL3/MIP‑1alpha in lipopolysaccharide (LPS)‑induced brain injury, and investigate whether the MAPKs and NF‑kappaB regulate CCL3/MIP‑1alpha expression. We firstly examined the patterns of CCL3/ MIP‑1alpha expression and phosphorylation of MAPKs in the brains of rats 6, 24, and 72 h after LPS administration. Additionally, LPS‑treated rats were administered an anti‑MIP‑1alpha neutralizing antibody, and the microglial reaction and the expression of both cyclooxygenase‑2 and inducible nitric oxide synthase (iNOS) were analyzed. We finally evaluated the effect of an inhibitor of P38 MAPK, an inhibitor of ERK1/2, or an inhibitor of NF‑kappaB, on the levels of CCL3/MIP‑1alpha protein and numbers of microglia in the brain. In the observation period, LPS induced CCL3/MIP‑1alpha expression, which localized to OX‑42‑labeled microglia, leading to time‑dependent increases in the phosphorylation of P38 MAPK and ERK1/2. The expression pattern of induced CCL3/MIP‑1alpha was partly consistent with the phosphorylation of MAPKs (P38 MAPK, ERK1/2). Anti‑MIP‑1alpha attenuated microglial accumulation and the upregulation of cyclooxygenase‑2 and iNOS. The inhibition of P38 MAPK, ERK1/2, or NF‑kappaB signaling reduced the induced upregulation of CCL3/MIP‑1alpha and the microglial accumulation. Our data suggest that upregulated CCL3/MIP‑1alpha mediates the accumulation of microglia and the neuroinflammatory reaction, and its expression may be regulated by MAPKs and NF‑kappaB in LPS‑induced brain injury.

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