Cordycepin inhibits IL-1 -induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts

Noh, Eun‐Mi; Kim, J.-S.; Hur, Hyun; Park, B.-H.; Song, Eun-Kyung; Han, Myung‐Kwan; Kwon, Kang‐Beom; Yoo, Wan‐Hee; Shim, Ilseob; Lee, Se Joon; Youn, Hyun Jo; Lee, Y.-R.

doi:10.1093/rheumatology/ken417

Cited by 89 publications

(79 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Supporting our observations, cordycepin inhibits the phosphorylation of MAPK in macrophage cells (31). In our previous study, we reported that cordycepin inhibited MMP-1 and -3 expression by suppressing AP-1 activation through MAPK signaling pathway in rheumatoid arthritis synovial fibroblasts (32). Also, we have confirmed that TPA-induced MMP-9 expression was significantly inhibited by the selective inhibitor of ERK1/2 (PD98059) or JNK (SP600125) and partly inhibited by selective inhibitors of the p38 MAPK (SB203580) (data not shown), and previous studies support our data (30,33,34).…”

Section: Discussionsupporting

confidence: 87%

Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Noh

Youn²,

Jung³

et al. 2009

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in breast cancer cell invasion. NF-κB and AP-1 are known to induce MMP-9 expression. We investigated whether cordycepin, an NF-κB or AP-1 inhibitor, can modulate MMP-9 expression and cell invasion in MCF-7 cells. Toxicity of cordycepin was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MMP-9 expression was determined by real-time PCR, Zymography, and Western blot analysis. AP-1 activation was assayed by electrophoretic mobility shift assay (EMSA). MAPK signaling was evaluated by Western blotting with specific p-ERK, and ERK, p-p38, p38, p-JNK, JNK antibodies. Cordycepin suppressed AP-1 activation, but not NF-κB activation in 12-O-tetradecanoylpho-bol-13-acetate (TPA)-treated MCF-7 cells. Cordycepin inhibits TPA-induced MMP-9 expression and cell invasion by suppressing AP-1 activation. Also, cordycepin suppressed the MAPK signaling pathway. Cordycepin is a potent inhibitor of TPA-induced MMP-9 expression and blocks strongly the ability of AP-1 activation via MAPK signaling pathway in MCF-7 cells.

show abstract

Section: Discussionsupporting

confidence: 87%

Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Noh

Youn²,

Jung³

et al. 2009

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…These fungi are highly prized in Tibetan and Chinese traditional medicine and used for a large number of afflictions, including kidney, heart, and lung conditions such as asthma (Winkler 2010). A variety of studies indicate that cordycepin has clear biological activities, it is antiproliferative, antimetastatic, and anti-inflammatory, and it inhibits the unfolded protein response (Nakamura et al 2005;Lee et al 2009Lee et al , 2010Noh et al 2009;Wong et al 2010;Cheng et al 2011;Kim et al 2011;Kitamura et al 2011). Because of its structure, cordycepin could potentially interfere with any process requiring adenosine or ATP.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of polyadenylation reduces inflammatory gene induction

Kondrashov

Meijer

Barthet-Barateig

et al. 2012

RNA

View full text Add to dashboard Cite

Cordycepin (39 deoxyadenosine) has long been used in the study of in vitro assembled polyadenylation complexes, because it terminates the poly(A) tail and arrests the cleavage complex. It is derived from caterpillar fungi, which are highly prized in Chinese traditional medicine. Here we show that cordycepin specifically inhibits the induction of inflammatory mRNAs by cytokines in human airway smooth muscle cells without affecting the expression of control mRNAs. Cordycepin treatment results in shorter poly(A) tails, and a reduction in the efficiency of mRNA cleavage and transcription termination is observed, indicating that the effects of cordycepin on 39 processing in cells are similar to those described in in vitro reactions. For the CCL2 and CXCL1 mRNAs, the effects of cordycepin are post-transcriptional, with the mRNA disappearing during or immediately after nuclear export. In contrast, although the recruitment of RNA polymerase II to the IL8 promoter is also unaffected, the levels of nascent transcript are reduced, indicating a defect in transcription elongation. We show that a reporter construct with 39 sequences from a histone gene is unaffected by cordycepin, while CXCL1 sequences confer cordycepin sensitivity to the reporter, demonstrating that polyadenylation is indeed required for the effect of cordycepin on gene expression. In addition, treatment with another polyadenyation inhibitor and knockdown of poly(A) polymerase a also specifically reduced the induction of inflammatory mRNAs. These data demonstrate that there are differences in the 39 processing of inflammatory and housekeeping genes and identify polyadenylation as a novel target for anti-inflammatory drugs.

show abstract

“…As individual response to drugs can vary, and as potential side effects remain one of the problems for long-term use of NSAIDs, phytochemicals are potential candidates as a novel agent to prevent inflammation for the treatment of many diseases, including OA [26]. Cordycepin, a nucleoside derivative isolated from Cordyceps, is reported to exert inhibitory effects on macrophages and RA synovial fibroblasts due to its antiinflammatory effect [12,16]. In this study, we evaluated the role of cordycepin in inflammatory responses in human articular chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Cordycepin has also been studied for antitumor [13], antidiabetic [14], and renoprotective effects [15]. Noh et al [16] demonstrated that cordycepin has anti-rheumatic and antiinflammatory effects on IL1β-stimulated rheumatoid arthritis synovial fibroblasts (RASFs). Shin et al [17] discovered that cordycepin could suppress expression of diabetes-regulating genes by inhibiting lipopolysaccharide-induced inflammation in macrophages.…”

Section: Introductionmentioning

confidence: 99%

Cordycepin prevented IL-β-induced expression of inflammatory mediators in human osteoarthritis chondrocytes

Ying

Lei

Chen

et al. 2013

International Orthopaedics (SICOT)

View full text Add to dashboard Cite

Purpose Cordycepin, a nucleoside derivative isolated from Cordyceps, has been reported to exert anti-inflammatory, antitumor, antidiabetic and renoprotective effects. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. This study aimed to assess the effects of cordycepin on human OA chondrocytes. Methods In this study, human OA chondrocytes were pretreated with cordycepin at 10, 50 or 100 μM and subsequently stimulated with interleukin-1β (IL-1β) (5 ng/ml) for 24 h. Production of prostaglandin E 2 (PGE2) and nitric oxide (NO) were evaluated by the Griess reaction and an enzymelinked immunosorbent assay (ELISA). Gene expression of matrix metalloproteinase (MMP)-13, IL-6, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) was measured by real-time polymerase chain reaction (PCR). MMP-13 and IL-6 proteins in culture medium were determined using cytokine-specific ELISA. Western immunoblotting was used to analyse the iNOS and COX-2 protein production in culture medium. Nuclear factor kappa-B (NF-κB) activity regulation was explored using Western immunoblotting. Results Pretreatment with cordycepin significantly inhibited the production of PGE2 and NO induced by IL-1β. Cordycepin also significantly decreased the IL-1β-stimulated gene expression and production of MMP-13, IL-6, iNOS and COX-2 in OA chondrocytes. Pretreatment with cordycepin attenuated IL-1β-induced activation of NF-κB by suppressing degradation of its inhibitory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α) in the cytoplasm. Conclusions We show for the first time the anti-inflammatory activity of cordycepin in human OA chondrocytes. Thus, with this unique profile of actions, cordycepin may prove to be a potentially attractive and new therapeutic/preventive agent for OA.

show abstract

Cordycepin inhibits IL-1 -induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts

Abstract: Cordycepin is a potent inhibitor of IL-1beta-induced chemokine production and MMP expression and strongly blocks the p38/JNK/AP-1 signalling pathway in RASFs.

Cited by 89 publications

References 43 publications

Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Inhibition of polyadenylation reduces inflammatory gene induction

Cordycepin prevented IL-β-induced expression of inflammatory mediators in human osteoarthritis chondrocytes

Contact Info

Product

Resources

About