IMM-H004 Protects against Cerebral Ischemia Injury and Cardiopulmonary Complications via CKLF1 Mediated Inflammation Pathway in Adult and Aged Rats.

Abstract

(1) Background: Chemokine-like factor 1 (CKLF1) is a chemokine with potential to be a target for stroke therapy. Compound IMM-H004 is a novel coumarin derivative screened from a CKLF1/C-C chemokine receptor type 4 (CCR4) system and has been reported to improve cerebral ischemia/reperfusion injury. This study aims to investigate the protective effects of IMM-H004 on cerebral ischemia injury and its infectious cardiopulmonary complications in adult and aged rats from the CKLF1 perspective. (2) Methods: The effects of IMM-H004 on the protection was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining, behavior tests, magnetic resonance imaging (MRI) scans, enzyme-linked immunosorbent assay (ELISA), Nissl staining, histo-pathological examination, and cardiopulmonary function detection. Immunohistological staining, immunofluorescence staining, quantitative real-time PCR (qPCR), and western blotting were used to elucidate the underlying mechanisms. (3) Results: IMM-H004 protects against cerebral ischemia induced brain injury and its cardiopulmonary complications, inhibiting injury, and inflammation through CKLF1-dependent anti-inflammation pathway in adult and aged rats. IMM-H004 downregulates the amount of CKLF1, suppressing the followed inflammatory response, and further protects the damaged organs from ischemic injury. (4) Conclusions: The present study suggested that the protective mechanism of IMM-H004 is dependent on CKLF1, which will lead to excessive inflammatory response in cerebral ischemia. IMM-H004 could also be a therapeutic agent in therapy for ischemic stroke and cardiopulmonary complications in the aged population.

• Authors: Qidi Ai, Chen Chen, Shifeng Chu, Yun Luo, Zhao Zhang, Shuai Zhang, Pengfei Yang, Yan Gao, Xiaoling Zhang, Naihong Chen
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 7 (Apr 03 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30987181 (Publication Type: Journal Article)

Chemical References

• Chemokines
• Cklf protein, rat
• Coumarins
• IMM-H004
• MARVEL Domain-Containing Proteins
• Neuroprotective Agents

Topics

• Aging (pathology)
• Animals
• Brain Injuries (drug therapy, etiology, pathology)
• Brain Ischemia (complications, drug therapy)
• Chemokines (metabolism)
• Coumarins (administration & dosage, chemistry, pharmacology, therapeutic use)
• Inflammation (metabolism, pathology)
• Lung (pathology)
• MARVEL Domain-Containing Proteins (metabolism)
• Male
• Myocardium (pathology)
• Neuroprotective Agents (administration & dosage, pharmacology, therapeutic use)
• Rats, Sprague-Dawley
• Stroke (complications)