IL-10 inhibits apoptosis in brain tissue around the hematoma after ICH by inhibiting proNGF

Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):3005-3011. doi: 10.26355/eurrev_201904_17582.

Abstract

Objective: To explore the roles of interleukin-10 (IL-10), proNGF and p75NTR in apoptosis of brain tissues induced by intracerebral hemorrhage (ICH).

Patients and methods: According to the time of sample collection after ICH, brain tissue samples were divided into < 6 h group, 6-24 h group (including 24 h), 24-72 h group (including 72 h) and > 72 h group. Meanwhile, 10 tissues that dropped from the beginning at the cortical stoma (distal part of the hematoma) were harvested as controls. AI in brain tissues around the hematoma after ICH was calculated based on TUNEL staining. Expression levels of IL-10, proNGF and p75NTR in brain tissues were determined by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Protein expressions of Bcl-2 and Bax were detected by Western blot. Rat cortical astrocytes were harvested and cultured in vitro. After transfection of IL-10 overexpression plasmid, expression levels of IL-10, proNGF and p75NTR were detected by Western blot.

Results: AI increased in 6-24 h group, 24-72 h group and > 72 h group compared with < 6 h group and control group, which achieved the peak at 24-72 h. However, no significant difference in AI was observed between < 6 h group and control group. With the prolongation of ICH, IL-10 level gradually decreased and achieved the lowest level at 24-72 h. After 72 h, IL-10 level began to increase. Additionally, mRNA and protein levels of proNGF and p75NTR started to upregulate within 6 h of ICH, achieveing the peak at 24-72 h. Bcl-2 level gradually decreased after 6 h of ICH, while Bax level increased. We did not found significant difference in mRNA and protein levels of IL-10 in brain tissues around hematoma between < 6 h group and control group. With the prolongation of ICH, IL-10 level gradually decreased and achieved the lowest level at 24-72 h. After 72 h, IL-10 level began to increase. Transfection with IL-10 overexpression plasmid in rat astrocytes markedly downregulated protein levels of proNGF and p75NTR compared with those of controls.

Conclusions: IL-10 expression is downregulated in brain tissues around the hematoma after ICH. IL-10 alleviates inflammation and apoptosis by inhibiting levels of proNGF, p75NTR and Bax/Bcl-2, thus protecting brain tissue after ICH.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Animals, Newborn
  • Apoptosis / physiology*
  • Brain / metabolism*
  • Brain / pathology
  • Cells, Cultured
  • Cerebral Hemorrhage / genetics
  • Cerebral Hemorrhage / metabolism*
  • Cerebral Hemorrhage / pathology
  • Female
  • Hematoma / genetics
  • Hematoma / metabolism*
  • Hematoma / pathology
  • Humans
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / genetics
  • Male
  • Middle Aged
  • Nerve Growth Factor / antagonists & inhibitors
  • Nerve Growth Factor / biosynthesis*
  • Nerve Growth Factor / genetics
  • Protein Precursors / antagonists & inhibitors
  • Protein Precursors / biosynthesis*
  • Protein Precursors / genetics
  • Rats
  • Rats, Wistar

Substances

  • IL10 protein, human
  • Protein Precursors
  • pro-nerve growth factor, human
  • Interleukin-10
  • Nerve Growth Factor