Updates in understanding the role of cyclophilin A in leukocyte chemotaxis

Dawar, Farman Ullah; Wu, Junjie; Zhao, Lijuan; Khattak, Muhammad Nasir Khan; Mei, Jie; Lin, Li

doi:10.1189/jlb.3ru1116-477r

Cited by 37 publications

(32 citation statements)

References 56 publications

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“…virus infection), activates and attracts leukocytes via its receptor CD147 to the stimulus site. 15 We demonstrated that anti-CD147 antibody could attenuate the chemotactic index of T cells induced by CyPA. 17 Multiple cytokines and chemokines increased significantly in patients with COVID-19, which was significantly correlated with pulmonary inflammation index of chest CT imaging.…”

Section: Discussionmentioning

confidence: 75%

“…13 CD147 is also presented in activated inflammatory cells and participates the regulation of cytokine secretion and leukocytes chemotaxis by binding with cyclophilin A (CyPA). 14,15 CyPA is a proinflammatory cytokine that is up-regulated in response to virus infection. 16 Our previous studies demonstrated that antibody targeting CD147 inhibited CyPA-induced T cell chemotaxis thus attenuating the local inflammation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

Bian

Zheng

Ding

et al. 2020

Preprint

140

135

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Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

Bian

Zheng

Ding

et al. 2020

Preprint

140

135

View full text Add to dashboard Cite

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“…Cyclophilin A (CypA) is a cytoplasmic peptidyl‐prolyl cis/trans isomerase and has diverse functions in biological processes, including protein folding, signal transduction, transcription regulation, and cell cycle regulation . CypA is also involved in many diseases such as cancer, cardiovascular infection, and viral infection …”

Section: Acknowledgmentsmentioning

confidence: 99%

NMR Analysis of the Interaction between Cyclophilin A and RIG‐I

Hwang

Kim

Lee

et al. 2019

Bulletin Korean Chem Soc

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“…15 CyPA acts as a pro-inflammatory mediator and is usually secreted by leukocytes, endothelial cells, and vascular smooth muscle cells, which further guide inflammatory cells infiltrating the stimulus site. [20][21][22] Extracellular CyPA is involved in biologic processes, including intracellular signaling, transcription, inflammation, and chemotaxis. 23,24 CyPA is also related to various diseases including periodontitis.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast‐enhanced cyclophilin A releasing from U937 cell upregulates MMP‐2 in gingival fibroblast

Kuo

Lin

Chen

et al. 2020

J of Periodontal Research

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Objective This in vitro study aimed to evaluate the expression of cyclophilin A (CyPA) in U937 monocytic cells after coculturing with the human gingival fibroblasts (HGFs) and the effect of CyPA on the augmentation of MMP‐2 expression in the coculture environment. Background Leukocyte infiltration in gingival connective tissue is one of the major findings in the lesions of inflammatory periodontal diseases. A crosstalk between the resident gingival fibroblasts and the recruited inflammatory cells that promote the expression of matrix metalloproteinases (MMPs) was proposed based on recent findings, whereas the cluster of differentiation 147 (CD147)‐CyPA pathway was suggested to be involved with the crosstalk. Material and Methods CyPA was released into media, in the independent or transwell coculture of HGF and U937 cells, as determined by enzyme‐linked immunosorbent assay, whereas intracellular mRNA expressions for CyPA and MMP‐2 were examined by quantitative real‐time polymerase chain reaction, in the transwell coculture or conditional medium models. Zymography was conducted to analyze the activities of pro‐MMP‐2/MMP‐2 released into the media. Results (a) A significantly increased CyPA protein level was observed in the transwell coculture media compared with that in the independent culture. (b) The transwell coculture‐enhanced mRNA expression for CyPA was noticed in U937 cells but not in HGFs. After adding with HGF‐conditioned medium, the mRNA enhancement in U937 cells occurred in a dose‐dependent manner. (c) Although the MMP‐2 activities significantly increased after transwell coculturing, the MMP‐2 mRNA enhancement was observed only in HGFs. (d) Exogenous CyPA could enhance MMP‐2 activities in HGFs in a dose‐dependent manner. However, the CyPA antagonist reduced the MMP‐2 activities in the transwell cocultures. (e) Moreover, the CyPA‐enhanced MMP‐2 activity in HGF was decreased significantly by the pathway inhibitor for c‐Jun amino‐terminal kinase (JNK). Conclusion Based on the present findings, we suggest that gingival fibroblasts could enhance the CyPA release from U937 cells, via the JNK pathway, resulting in MMP‐2 enhancement in fibroblasts. The finding shed light on a new mechanism of cellular interaction involving MMP‐2 and CyPA, in two cells.

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Updates in understanding the role of cyclophilin A in leukocyte chemotaxis

Cited by 37 publications

References 56 publications

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

NMR Analysis of the Interaction between Cyclophilin A and RIG‐I

Fibroblast‐enhanced cyclophilin A releasing from U937 cell upregulates MMP‐2 in gingival fibroblast

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