PMID- 33521454
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210202
IS  - 2470-1343 (Electronic)
IS  - 2470-1343 (Linking)
VI  - 6
IP  - 3
DP  - 2021 Jan 26
TI  - Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like 
      Synoviocytes (FLS).
PG  - 2149-2155
LID - 10.1021/acsomega.0c05281 [doi]
AB  - Pro-inflammatory cytokines, such as the IL-18-induced inflammatory response and 
      associated damage in fibroblast-like synoviocytes (FLS), play an important role 
      in the pathogenesis of rheumatoid arthritis (RA). Roflumilast, an inhibitor of 
      phosphodiesterase-4 (PDE-4), has been licensed for the treatment of chronic 
      obstructive pulmonary disease (COPD). However, it is unknown whether roflumilast 
      possesses a protective effect against the IL-18-induced inflammatory response in 
      FLS. We found that roflumilast attenuated IL-18-induced oxidative stress by 
      reducing the production of reactive oxygen species and malondialdehyde (MDA) in 
      MH7A fibroblast-like synoviocytes (FLS). Additionally, roflumilast prevented 
      IL-18-induced expressions and secretions of pro-inflammatory cytokines such as 
      IL-6, IL-8, and TNF-alpha. Importantly, we found that roflumilast inhibited 
      IL-18-induced expressions of chemokines such as CCL5, CXCL9, and CXCL10. Further, 
      roflumilast inhibited the expression of extracellular matrix degradative enzymes, 
      such as matrix metalloproteinase-3 (MMP-3) and MMP-13. Mechanistically, we found 
      that roflumilast suppressed the activation of the transcriptional factor AP-1 and 
      NF-kappaB. Our results suggest that roflumilast might be a potential therapeutic 
      agent for the treatment of RA.
CI  - (c) 2021 American Chemical Society.
FAU - Zhong, Bing
AU  - Zhong B
AD  - Department of Orthopaedics, YiLing Hospital, No. 32, Donghu Avenue, Yichang 
      443100, Hubei, China.
FAU - Guo, Shuanghong
AU  - Guo S
AD  - Department of Orthopaedics, YiLing Hospital, No. 32, Donghu Avenue, Yichang 
      443100, Hubei, China.
FAU - Yang, Zhongai
AU  - Yang Z
AD  - Central Hospital of Yichang, Yichang 443003, Hubei, China.
FAU - Han, Li
AU  - Han L
AD  - Department of Medicine, China Three Gorges University, Yichang 443002, Hubei, 
      China.
FAU - Du, Junsheng
AU  - Du J
AD  - Department of Orthopaedics, YiLing Hospital, No. 32, Donghu Avenue, Yichang 
      443100, Hubei, China.
FAU - Chen, Jin
AU  - Chen J
AD  - Department of Orthopaedics, YiLing Hospital, No. 32, Donghu Avenue, Yichang 
      443100, Hubei, China.
FAU - Dun, Xianli
AU  - Dun X
AD  - Department of Orthopaedics, YiLing Hospital, No. 32, Donghu Avenue, Yichang 
      443100, Hubei, China.
FAU - Wang, Guangyong
AU  - Wang G
AD  - Department of Orthopaedics, YiLing Hospital, No. 32, Donghu Avenue, Yichang 
      443100, Hubei, China.
LA  - eng
PT  - Journal Article
DEP - 20210114
PL  - United States
TA  - ACS Omega
JT  - ACS omega
JID - 101691658
PMC - PMC7841938
COIS- The authors declare no competing financial interest.
EDAT- 2021/02/02 06:00
MHDA- 2021/02/02 06:01
PMCR- 2021/01/14
CRDT- 2021/02/01 06:02
PHST- 2020/10/29 00:00 [received]
PHST- 2020/12/11 00:00 [accepted]
PHST- 2021/02/01 06:02 [entrez]
PHST- 2021/02/02 06:00 [pubmed]
PHST- 2021/02/02 06:01 [medline]
PHST- 2021/01/14 00:00 [pmc-release]
AID - 10.1021/acsomega.0c05281 [doi]
PST - epublish
SO  - ACS Omega. 2021 Jan 14;6(3):2149-2155. doi: 10.1021/acsomega.0c05281. eCollection 
      2021 Jan 26.