PMID- 32990777
OWN - NLM
STAT- MEDLINE
DCOM- 20201130
LR  - 20201217
IS  - 1420-908X (Electronic)
IS  - 1023-3830 (Linking)
VI  - 69
IP  - 12
DP  - 2020 Dec
TI  - Roflumilast prevents lymphotoxin alpha (TNF-beta)-induced inflammation activation and 
      degradation of type 2 collagen in chondrocytes.
PG  - 1191-1199
LID - 10.1007/s00011-020-01404-3 [doi]
AB  - BACKGROUND AND PURPOSE: Osteoarthritis (OA) is a chronic disease accompanied by 
      severe inflammation. The inflammation activation in the chondrocytes and the 
      degradation of the extracellular matrix were reported to be involved in the 
      progress of OA. Roflumilast is a selective PDE4 inhibitor used for treating 
      chronic obstructive pulmonary disease (COPD) and exerts significant 
      anti-inflammation effects. The present study aims to investigate the effects of 
      Roflumilast on tumor necrosis factor-beta (TNF-beta)-induced inflammation activation 
      and degradation of type 2 collagen in chondrocytes. METHODS: TNF-beta was used to 
      establish the in-vitro inflammation model on ATDC5 chondrocytes. Quantitative 
      real-time polymerase chain reaction (QRT-PCR) and western blot were used to 
      determine the expression level of tumor necrosis factor receptor 2 (TNFR2), 
      cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix 
      metalloproteinase 3 (MMP-3), matrix metalloproteinase 13 (MMP-13), type 2 
      collagen and nuclear factor kappa B (NF-kappaB) p65. The release of prostaglandin E2 
      (PGE(2)), MMP-3, and MMP-13 were evaluated by ELISA. The production of NO was 
      determined by DAF-FM DA staining and the function of the NF-kappaB promoter was 
      evaluated by Luciferase activity assay. RESULTS: TNFR2 and COX-2 were upregulated 
      and the release of PGE(2) was promoted by TNF-beta stimulation, which were all 
      inhibited by Roflumilast. Roflumilast suppressed the promoted iNOS expression and 
      NO production induced by TNF-beta. MMP-3 and MMP-13 were up-regulated, and type 2 
      collagen was down-regulated by TNF-beta stimulation, which were all reversed by 
      Roflumilast. Roflumilast inhibited the promoted releasing of Interleukin-8 (IL-8) 
      and Interleukin-12 (IL-12), expression of up-regulated NF-kappaB, and activation of 
      NF-kappaB transcriptional activity induced by TNF-beta. CONCLUSION: Roflumilast may 
      prevent TNF-beta-induced inflammation activation and degradation of type 2 collagen 
      in chondrocytes.
FAU - Zhao, Jingtong
AU  - Zhao J
AD  - Department of Central Laboratory, China-Japan Union Hospital of Jilin University, 
      No. 126 Xiantai Street, Changchun, 130033, China.
FAU - Duan, Lian
AU  - Duan L
AD  - Department of Central Laboratory, China-Japan Union Hospital of Jilin University, 
      No. 126 Xiantai Street, Changchun, 130033, China.
FAU - Wang, Renxiang
AU  - Wang R
AD  - Department of Radiotherapy, Tonghua Central Hospital, Tonghua, 134001, China.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union 
      Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, 
      China. liuyi17@mails.jlu.edu.cn.
FAU - Jiang, Jinlan
AU  - Jiang J
AUID- ORCID: 0000-0002-5733-1615
AD  - Department of Central Laboratory, China-Japan Union Hospital of Jilin University, 
      No. 126 Xiantai Street, Changchun, 130033, China. jiangjinlan@jlu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200929
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Aminopyridines)
RN  - 0 (Benzamides)
RN  - 0 (Collagen Type II)
RN  - 0 (Cyclopropanes)
RN  - 0 (Cytokines)
RN  - 0 (Lymphotoxin-alpha)
RN  - 0 (Phosphodiesterase 4 Inhibitors)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0P6C6ZOP5U (Roflumilast)
SB  - IM
MH  - Aminopyridines/*pharmacology
MH  - Benzamides/*pharmacology
MH  - Cell Line
MH  - Chondrocytes/drug effects/*metabolism
MH  - Collagen Type II/*metabolism
MH  - Cyclopropanes/pharmacology
MH  - Cytokines/metabolism
MH  - Extracellular Matrix/drug effects
MH  - Humans
MH  - Inflammation/*chemically induced/*prevention & control
MH  - *Lymphotoxin-alpha
MH  - Phosphodiesterase 4 Inhibitors/*pharmacology
MH  - Receptors, Tumor Necrosis Factor, Type II/metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Chondrocytes
OT  - Extracellular matrix
OT  - Inflammation
OT  - Osteoarthritis
OT  - Roflumilast
OT  - TNF-beta
EDAT- 2020/09/30 06:00
MHDA- 2020/12/01 06:00
CRDT- 2020/09/29 12:37
PHST- 2020/05/28 00:00 [received]
PHST- 2020/09/15 00:00 [accepted]
PHST- 2020/09/04 00:00 [revised]
PHST- 2020/09/30 06:00 [pubmed]
PHST- 2020/12/01 06:00 [medline]
PHST- 2020/09/29 12:37 [entrez]
AID - 10.1007/s00011-020-01404-3 [pii]
AID - 10.1007/s00011-020-01404-3 [doi]
PST - ppublish
SO  - Inflamm Res. 2020 Dec;69(12):1191-1199. doi: 10.1007/s00011-020-01404-3. Epub 
      2020 Sep 29.