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

• Autorzy: Zhu X. , Wei D. , Chen O. , Zhang Z. , Xue J. , Huang S. , Zhu W. , Wang Y.
• Języki publikacji: EN

Abstrakty

EN

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.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2016
• Tom: 76
• Numer: 4
• Opis fizyczny: p.304-317,fig.,ref.

Twórcy

autor

Zhu X.

• Department of Pediatrics, Second Hospital of Shandong University, Jinan, China

autor

Wei D.

• Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, China

autor

Chen O.

• Department of Pediatrics, Second Hospital of Shandong University, Jinan, China

autor

Zhang Z.

• Department of Pediatrics, Second Hospital of Shandong University, Jinan, China

autor

Xue J.

• Department of Pediatrics, Second Hospital of Shandong University, Jinan, China

autor

Huang S.

• Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Jinan, China

autor

Zhu W.

• Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, China

autor

Wang Y.

• Department of Pediatrics, Second Hospital of Shandong University, Jinan, China

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