Alantolactone suppresses inducible nitric oxide synthase and cyclooxygenase-2 expression by down-regulating NF-κB, MAPK and AP-1 via the MyD88 signaling pathway in LPS-activated RAW 264.7 cells

Chun, Jaemoo; Choi, Ran Joo; Khan, Salman; Lee, Dong-Sung; Kim, Youn‐Chul; Nam, Young-Joo; Lee, Dong‐Ung; Kim, Yeong Shik

doi:10.1016/j.intimp.2012.08.011

Cited by 170 publications

(121 citation statements)

References 33 publications

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“…20 Activated TAK1 also phosphorylates MAPKs, including p38, ERK1/2 and JNK, to induce the activation of AP-1. 21,22 ERK1/2 primarily regulates cell differentiation and proliferation, while p38 and JNK play an important role in inflammation, the stress response and cell survival/apoptosis. To determine whether MAPKs have an effect on the activation of ATF4 upon LPS stimulation, we performed experiments using four kinase inhibitors.…”

Section: Jnk Is Involved In the Activation Of Atf4 Via Tlr4 Signalingmentioning

confidence: 99%

ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes

et al. 2012

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Toll-like receptors (TLRs) are sentinels of the host defense system, which recognize a large number of microbial pathogens. The host defense system may be inefficient or inflammatory diseases may develop if microbial recognition by TLRs and subsequent TLR-triggered cytokine production are deregulated. Activating transcription factor 4 (ATF4), a member of the ATF/CREB transcription factor family, is an important factor that participates in several pathophysiological processes. In this report, we found that ATF4 is also involved in the TLR-mediated innate immune response, which participates in TLR4 signal transduction and mediates the secretion of a variety of cytokines. We observed that ATF4 is activated and translocates to the nucleus following lipopolysaccharide (LPS) stimulation via the TLR4-MyD88-dependent pathway. Additionally, a cytokine array assay showed that some key inflammatory cytokines, such as IL-6, IL-8 and RANTES, are positively regulated by ATF4. We also demonstrate that c-Jun directly binds to ATF4, thereby promoting the secretion of inflammatory cytokines. Taken together, these results indicate that ATF4 acts as a positive regulator in TLR4-triggered cytokine production.

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Section: Jnk Is Involved In the Activation Of Atf4 Via Tlr4 Signalingmentioning

confidence: 99%

ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes

et al. 2012

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“…Costunolide inhibited the activation of Akt and NF-kB and the expression of antiapoptotic factors B-cell lymphoma-extra large (Bcl-xL) and X-linked inhibitor of apoptosis protein (XIAP) in 11Z cells (69)(70)(71), magnolol inhibits ERK1/2 phosphorylation and NF-kB translocation (72,73), PI3K/Akt/caspase and Fas-L/NF-kB signaling pathways might account for the responses of A375-S2 cell death induced by evodiamine (74,75). Oridonin (76), alantolactone (77,78), isoalantolactone (79), casticin (80), pseudolaric acid B (81), and jaceosidin (82), each of them has an inhibitory effect on NF-kB and its associated proteins. These compounds may inhibit one or more steps in NF-kB signaling pathway and its upstream growth factor receptors that activate the signaling cascade, translocation of NF-kB to the nucleus, DNA binding of the dimers, or interactions with the basal transcriptional machinery.…”

Section: Nf-kb and Its Family Member Pathwaymentioning

confidence: 99%

Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature

Millimouno

Dong

Liu

et al. 2014

Cancer Prevention Research

236

168

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Although the incidences are increasing day after day, scientists and researchers taken individually or by research group are trying to fight against cancer by several ways and also by different approaches and techniques. Sesquiterpenes, flavonoids, alkaloids, diterpenoids, and polyphenolic represent a large and diverse group of naturally occurring compounds found in a variety of fruits, vegetables, and medicinal plants with various anticancer properties. In this review, our aim is to give our perspective on the current status of the natural compounds belonging to these groups and discuss their natural sources, their anticancer activity, their molecular targets, and their mechanism of actions with specific emphasis on apoptosis pathways, which may help the further design and conduct of preclinical and clinical trials. Unlike pharmaceutical drugs, the selected natural compounds induce apoptosis by targeting multiple cellular signaling pathways including transcription factors, growth factors, tumor cell survival factors, inflammatory cytokines, protein kinases, and angiogenesis that are frequently deregulated in cancers and suggest that their simultaneous targeting by these compounds could result in efficacious and selective killing of cancer cells. This review suggests that they provide a novel opportunity for treatment of cancer, but clinical trials are still required to further validate them in cancer chemotherapy. Cancer Prev Res; 7(11);

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“…In addition, they are involved in the modulation of NF-κB and AP-1 activities (Chun et al, 2012;Endale et al, 2013). Thus, we examined the effects of MSE on the …”

Section: Mse Inhibits Lps-induced Mapk Phosphorylationmentioning

confidence: 99%

“…Furthermore, MAPKs are involved in the expression of proinflammatory mediators, including iNOS, COX-2, and inflammatory cytokines. LPS-stimulated inflammation leads to the activation of MAPK pathways, which in turn mediate the expression of several transcription factors, including NF-κB and AP-1 (Chun et al, 2012;Endale et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Maydis Stigma Elicits Analgesia and Blocks Edema in Mice and Inhibits Inflammation in Macrophages

Jeong

Cho

et al. 2017

Am. J. Chin. Med.

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Maydis Stigma (MS) is an herb traditionally used in many parts of the world. Previous studies have reported that MS plays a role in several biological activities, including antidiabetic and anticancer activities. However, the effects of a MS ethanolic extract (MSE) on the anti-inflammatory cellular mechanism remain unclear. Here, we investigated the antiinflammatory properties of MSE and its molecular mechanism both in vitro and in vivo. The effects of MSE on the production of inflammatory mediators, cytokines, and related proteins and the identification of target genes were determined using LPS-stimulated macrophages. We also determined the analgesic and anti-inflammatory effects of MSE by examining acetic acid-induced writhing responses and xylene-induced ear edema in mice. Our results indicated that MSE markedly decreased iNOS and COX-2 levels without causing cytotoxicity and suppressed the secretion of NO in LPS-stimulated macrophages. MSE also inhibited the production of proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, and induced the expression of HO-1. Moreover, MSE treatment significantly reduced the LPS-stimulated activation of MAPK, NF-κB, and AP-1. Furthermore, MSE exerted an analgesic effect on the acetic acid-induced abdominal writhing response test and an anti-inflammatory effect on xylene-induced ear edema in ICR mice. Finally, we investigated the components of MSE using UPLC-ESI-MS and found that it contains the maysin as a marker component. Overall, these observations demonstrate that MSE has anti-inflammatory and antinociceptive effects both in vitro and in vivo, which may provide new scientific evidence for its use as a potential therapeutic agent for the treatment of inflammation.

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Alantolactone suppresses inducible nitric oxide synthase and cyclooxygenase-2 expression by down-regulating NF-κB, MAPK and AP-1 via the MyD88 signaling pathway in LPS-activated RAW 264.7 cells

Cited by 170 publications

References 33 publications

ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes

ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes

Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature

Maydis Stigma Elicits Analgesia and Blocks Edema in Mice and Inhibits Inflammation in Macrophages

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