Camostat mesilate inhibits pro-inflammatory cytokine secretion and improves cell viability by regulating MFGE8 and HMGN1 in lipopolysaccharide-stimulated DF-1 chicken embryo fibroblasts

Camostat mesilate (CM) possesses potential anti-viral and anti-inflammatory activities. However, it remains unknown whether CM is involved in lipopolysaccharide (LPS)-mediated inflammatory responses and cell injury. In this project, differentially expressed proteins (DEPs, fold change ≥ 1.2 or ≤ 0.83 and Q value ≤ 0.05) in response to LPS stimulation alone or in combination with CM were identified through tandem mass tags (TMT)/mass spectrometry (MS)-based proteomics analysis in DF-1 chicken embryo fibroblasts. The mRNA expression levels of filtered genes were determined by RT-qPCR assay. The results showed that CM alleviated the detrimental effect of LPS on cell viability and inhibited LPS-induced TNF-α and IL-6 secretions in DF-1 chicken embryo fibroblasts. A total of 141 DEPs that might be involved in mediating functions of both LPS and CM were identified by proteomics analysis in DF-1 chicken embryo fibroblasts. LPS inhibited milk fat globule EGF and factor V/VIII domain containing (MFGE8) expression and induced high mobility group nucleosome binding domain 1 (HMGN1) expression, while these effects were abrogated by CM in DF-1 chicken embryo fibroblasts. MFGE8 knockdown facilitated TNF-α and IL-6 secretions , reduced cell viability, stimulated cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. HMGN1 loss did not influence TNF-α and IL-6 secretions, cell viability, and cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. In conclusion, CM exerted anti-inflammatory and pro-survival activities by regulating MFGE8 in LPS-stimulated DF-1 chicken embryo fibroblasts, deepening our understanding of the roles and molecular basis of CM in protecting against Gram-negative bacteria.

Foistar(Camostat mesylate) associated with the significant decrease in CRP levels compared to Kaletra(Lopinavir/Ritonavir) treatment in Korean mild COVID-19 pneumonic patients.

Background There is limited information due to absence of virus titer and symptom related changes. Nonetheless, this is the first comparative study between the use of Foistar (Camostat mesilate) and Kaletra (lopinavir/ritonavir) on COVID-19 infection. Methods Patients with confirmed SARS-CoV-2 infection by positive polymerase chain reaction (PCR) testing that were admitted to Seoul Medical Center (Seoul, South Korea) where is the largest public medical center in South Korea between August 1 and September 20, 2020 were included The data of the patients with pneumonia who received Foistar (Foistar group) during their hospitalization period were primarily collected, and the patients who received Kaletra (Kaletra group) during their hospitalization period were matched to have a similar age group to that of Foistar group so that three times the number of Foistar group patients were randomly selected into Kaletra group and their body temperature, CRP level, WBC count, and event of diarrhea were collected, accordingly. Results A total of 29 patients (7 Foistar group and 22 Kaletra group) was included. The median age was 69, and all had mild COVID-19 (WHO ordinal scale 3 or 4) on admission. 6 patients out of 7 patients (85.71%) from Foistar group who exhibited elevated CRP levels (CRP >0.4mg/dL) on admission have controlled their CRP levels to the normal range. In Kaletra group, 11 out of 18 patients (61.11%) have controlled their CRP levels to the normal range, and only 1 of 2 patients (50.00%) who had normal CRP level has maintained his or her normal CRP level. The difference in the white blood cell counts was not significant between two groups. None of the patients in the study had hyperkalemia. Conclusion This study has found a probable association of controlling inflammatory reactions and fever in COVID-19 patients with Foistar (camostat mesilate) use. In addition, there was no significant adverse drug event found from this study upon the Foistar use. These results may encourage the use of Foistar as a treatment option for the patients with mild to moderate COVID-19.