CKLF1 Aggravates Focal Cerebral Ischemia Injury at Early Stage Partly by Modulating Microglia/Macrophage Toward M1 Polarization Through CCR4

Chen, Chen; Chu, Shifeng; Ai, Qidi; Zhang, Zhao; Guan, Feifei; Wang, Shasha; Dong, Yixiao; Zhu, Jie; Jian, Wenxuan; Chen, Nai‐Hong

doi:10.1007/s10571-019-00669-5

Cited by 42 publications

(24 citation statements)

References 46 publications

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“…Chemokine-liked factor 1 (CKLF1) was found to increase expression of pro-inflammatory cytokines and decrease that of anti-inflammatory cytokines in ischemic lesions. CKLF1 was also found to modulate microglia/macrophages toward an M1 phenotypic polarization, thus aggravating the inflammatory response and contributing to a poor prognosis following ischemic stroke (105–107).…”

Section: Resident Glial Cells and Infiltrating Macrophages/monocytesmentioning

confidence: 99%

Immunoreactive Cells After Cerebral Ischemia

et al. 2019

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The immune system is rapidly activated after ischemic stroke. As immune cells migrate and infiltrate across the blood-brain barrier into the ischemic region, a cascade of cellular and molecular biological reactions occur, involving migrated immune cells, resident glial cells, and the vascular endothelium. These events regulate infarction evolution and thus influence the outcome of ischemic stroke. Most immune cells exert dual effects on cerebral ischemia, and some crucial cells may become central targets in ischemic stroke treatment and rehabilitation.

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Section: Resident Glial Cells and Infiltrating Macrophages/monocytesmentioning

confidence: 99%

Immunoreactive Cells After Cerebral Ischemia

et al. 2019

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“…The membranes were blocked with 5% skimmed milk for 1 h at room temperature, and then incubated at 4 ℃ for one night with the primary antibodies including rabbit anti-Arg-1 (1:1,000; Cell Signaling Technology); rabbit anti-iNOS (1:1,000; Abcam); anti-MK2 (1:500; Abcam), After three washes, the membranes were incubated with an HRP-coupled secondary antibody at room temperature for 1 h, and washed three times again for 10 min each at room temperature. Finally, all the membranes were imaged using densitometry (Bio-Rad, Hercules, CA, USA) and quantified with the densitometric analysis (Image J software, NIH) (10,11).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Arg-1 (Forward-TTGGGAAGACAGCAGAGGAG-3, Reverse-GTCAGTCCCTGGCTTATGGT), iNOS (Forward-CATGACTCCCAGCACAAAGG, Reverse-CTGGAACAGCACTCTCTTGC), MK2 (Forward-TTTCCTAACCCGGAGTGGTC, Reverse-CCATCGTTCCTTGTCCTCCT), TNF-a (Forward-TCTCTTCAAGGGACAAGGCT, Reverse-GGCAGAGAGGAGGTTGACTT), Bax (Forward-CAAGAAGCTGAGCGAGTGTC, Reverse-GTCCACGTCAGCAATCATCC), Bcl-2 (Forward-GCATGCGACCTCTGTTTGAT, Reverse-CAGGTATGCACCCAGAGTGA), IL-1 (Forward-AAGAGCCCATCCTCTGTGAC, Reverse-AGCTCATATGGGTCCGACAG), NF-KB (Forward-GACCCAGGAGTGTTCACAGA, Reverse-CTCAGCTGTGGAGTGAGACA), GAPDH (Forward-TGCCCCCATGTTTGTGATG, Reverse-TGTGGTCATGAGCCCTTCC) (10,11).…”

Section: Realtime Pcr Analysismentioning

confidence: 99%

Role of MK2 signaling pathway mediating microglia/macrophages polarization in chronic compression injury of cervical spinal cord

Song

Fang

et al. 2021

Ann Palliat Med

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Background: The role of inflammatory factors in the chronic compression injury of cervical spinal cord has drawn more attention recently, however, the mechanism of which is still unclear. In this study, microglia/ macrophages polarization in the inflammatory responses to the injury and its regulation by MK2 signaling pathway have been investigated.Methods: twy/twy mice at the age of 6-24 weeks were used in the animal model for the chronic compression of cervical spinal cord. ICR (Institute of Cancer Research) mice were used as the control group.MK2 inhibitor (PF-3644022, 30 mg/kg) was administrated intragastrically to twy/twy mice from weeks 20 to 24. The compression of cervical spinal cord was identified by CT/MRI. The cervical spinal cord between C2 and C3 of vertebral segments were investigated by Western blot and Real-time PCR. The animal behaviors were evaluated by BMS score.Results: Western blot and Real-time PCR showed that the expressions of iNOS and Arg-1 in the compressed spinal cord of twy/twy mice were significantly higher than those of the control group. After treatment with PF-3644022, the expression of Arg1 was increased while that of iNOS decreased. Realtime PCR revealed the increased expressions of inflammation related factors (such as IL-1β, NF-κB, TNF-α, MK2) and pro-apoptotic gene (Bax) except the decreased expression of anti-apoptotic gene (Bcl-2).Nevertheless, such increases were vanished after treatment of PF-3644022 except an increased expression of Bcl-2. The BMS score showed a reduced motor function of the twy/twy mice. The motor function was enhanced again with the treatment of PF-3644022.Conclusions: Microglia/macrophages polarization may be involved in the inflammatory response to the chronic compression of cervical spinal cord. It can be regulated by the MK2 signaling pathway. Therefore, it is possible to relieve the chronic compression of cervical spinal cord by regulating microglia/macrophages polarization through MK2 signaling pathway.

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“…Recently, they showed that CKLF1 could promote the polarization of microglia/macrophages towards M1 at early stage of cerebral ischemic injury, which would further deteriorate the inflammatory response. 50 Potential signaling pathways CKLF1 involved in CKLF1 can bind to CCR4 on the cell surface and play a series of biological roles. CCR4 is a seven-transmembrane G protein-coupled receptor, which is expressed in various tissues and located on the surface of T cells, NK cells, monocytes, and eosinophils.…”

Section: Relationships Between Cklf1 and Other Diseasesmentioning

confidence: 99%

Section: Biological Functions Of Cklf1mentioning

confidence: 99%

Chemokine-like factor 1: A promising therapeutic target in human diseases

Cai

Deng

Ming

et al. 2020

Exp Biol Med (Maywood)

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Chemokines are a family of small molecular-weight proteins, being well-known with their important roles in the process of allergic response, immune regulation, cell proliferation, and differentiation. Almost two decades ago, a novel member of this family, chemokine-like factor 1 (CKLF1) was identified. In recent years, it draws much attention of researchers because of its key roles in many types of tissues and its potential implications in a large number of diseases. Up to now, CKLF1 has been shown to have two main functions: broad-spectrum chemotactic activity, and proliferation- and differentiation-promoting abilities. In this review, we would introduce the basic structural features of CKLF1 and its biological functions, and then elaborate the relationships between CKLF1 and human diseases. The cell signaling pathways CKLF1 may be involved in would be discussed and summarized in details. Furthermore, we present the trials of CKLF1-targeted treatments in animal disease models, hoping to provide a few important insights about CKLF1 to both medical researchers and pharmacy, and finally conclude that CKLF1 is a potent, and very promising, therapeutic target. Impact statement CKLF1, a recently identified chemokine, has been reported by a number of studies to play important roles in quite many diseases. However, the potential pathways that CKLF1 may be involved are not manifested well yet. In our review, we showed the basic molecular structure and major functions of this novel chemokine, and implication in human diseases, such as tumors. To attract more attention, we summarized its signaling pathways and clearly present them in a set of figures. With the overview of the experimental trial of CKLF1-targeting medicines in animal models, we hope to provide a few important insights about CKLF1 to both medical researchers and pharmacy.

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CKLF1 Aggravates Focal Cerebral Ischemia Injury at Early Stage Partly by Modulating Microglia/Macrophage Toward M1 Polarization Through CCR4

Cited by 42 publications

References 46 publications

Immunoreactive Cells After Cerebral Ischemia

Immunoreactive Cells After Cerebral Ischemia

Role of MK2 signaling pathway mediating microglia/macrophages polarization in chronic compression injury of cervical spinal cord

Chemokine-like factor 1: A promising therapeutic target in human diseases

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