Novel role of IL-6/SIL-6R signaling in the expression of inducible nitric oxide synthase (iNOS) in murine B16, metastatic melanoma clone F10.9, cells

Kang, Keon Wook; Wagley, Yadav; Kim, Hyun Woo; Pokharel, Yuba Raj; Chung, Yoon Young; Chang, In Youb; Kim, Jong Joong; Moon, Jeong Seok; Kim, Youn Kyu; Nah, Seung Yeol; Kang, Hyung Sik; Oh, Jae Wook

doi:10.1016/j.freeradbiomed.2006.10.034

Cited by 16 publications

(11 citation statements)

References 67 publications

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“…The 5'-flanking region of the iNOS gene contains several cisregulatory sequences, including two copies of each of the NF-κB and TNF-α response elements. NF-κB plays a critical role in induction of iNOS by LPS [23,24]. Thus, suppression of NF-κB activation may explain the fall in NO production in RAW 264.7 cells treated with the WI extract.…”

Section: Discussionmentioning

confidence: 99%

A Leaf Methanolic Extract of Wercklea insignis Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Blocking the NF-κB Signaling Pathway in RAW 264.7 Macrophages

et al. 2011

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The biological activity of Wercklea insignis (WI) in inflammation and the underlying mechanisms of action of extracts of this plant are largely unknown. In the present study, we investigated the effects of a WI methanolic extract on lipopolysaccharide-stimulated inflammation in the mouse macrophage cell line, RAW 264.7. A WI methanolic extract significantly inhibited NO, PGE(2), IL-6, IL-1β, and TNF-α production in LPS-stimulated RAW 264.7 cells. Expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α were suppressed by the extract at both the mRNA and protein levels in lipopolysaccharide (LPS)-stimulated cells. Additionally, the attenuation of inflammatory responses in RAW 264.7 cells by the WI extract was closely associated with suppression of phosphorylation of mitogen-activated protein kinase (MAPK) molecules, including ERK, JNK1/2, and p38 MAPK and translocation of the nuclear factor (NF)-κB p65 subunit into the nucleus. The effect of WI extract was investigated against carrageenan-induced paw edema in female (20-25 g). Our results collectively indicate that the WI extract inhibits LPS-induced inflammatory responses by blocking the NF-κB signaling pathway in macrophages, supporting use of the extract as a therapeutic anti-inflammatory treatment.

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Section: Discussionmentioning

confidence: 99%

A Leaf Methanolic Extract of Wercklea insignis Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Blocking the NF-κB Signaling Pathway in RAW 264.7 Macrophages

et al. 2011

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“…Previous evidence suggests that the IL-6-IL-6R-gp130 complex stimulates MAPK activation and several MAPKs such as p38 and ERK. Activation of these pathways promotes the excitability of primary afferent neurons [16]; the relevance of these signaling pathways by IL-6R in pancreatitis induced pain states warrant further investigations.…”

Section: Discussionmentioning

confidence: 99%

“…When IL-6 reaches an IL-6-responsive cell, it binds to its specific receptor, IL-6R, that exists in both transmembrane and soluble forms [33]. Binding of IL-6 triggers an association of the IL-6R with the transducer protein, gp130 [12], initiating an intracellular cascade of phosphorylation of several signal proteins including Janus kinases, STAT factors [11] as well as the MAPKs [16;41]. Based on IL-6’s known role in inflammation and pain promoting properties we hypothesized that IL-6 might be an important mediator of pancreatitis-induced pain.…”

Section: Introductionmentioning

confidence: 99%

Reversal of pancreatitis-induced pain by an orally available, small molecule interleukin-6 receptor antagonist

Vardanyan

Melemedjian

Price

et al. 2010

Pain

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Pancreatic pain resulting from chronic inflammation of the pancreas is often intractable and clinically difficult to manage with available analgesics reflecting the need for more effective therapies. Mechanisms underlying pancreatitis pain are not well understood. Here, the possibility that interleukin-6 (IL-6) may promote pancreatitis pain was investigated with TB-2-081 (3-O-formyl-20R,21-epoxyresibufogenin, EBRF), a small molecule IL-6 receptor antagonist that was semi-synthetically derived from natural sources. The potential activity and mechanism of TB-2-081 was investigated following induction of persistent pancreatitis using dibutyltin dichloride (DBTC) in rats. TB-2-081 displaces binding of IL-6 to the human recombinant soluble IL-6 receptor with apparent high affinity and inhibits IL-6 mediated cell growth. Systemic or oral, but not intrathecal, administration of TB-2-081 reversed DBTC-induced abdominal hypersensitivity in a dose- and time-dependent manner. IL-6 levels were significantly upregulated in the dorsal root ganglia (DRG) of rats with pancreatitis on day 6 after DBTC injection. IL-6 enhanced capsaicin-evoked release of calcitonin gene related peptide from cultured DRG neurons was blocked by TB-2-081. Our data demonstrate that TB-2-081 acts as a systemically available and orally active small molecule IL-6 receptor antagonist. TB-2-081 effectively reduces pancreatitis-induced pain through peripheral mechanisms that are likely due to (a) increased expression of IL-6 in the DRG and (b) IL-6-mediated sensitization of nociceptive neurons. The activity of TB-2-081 implicates an important role for IL-6 in sustaining pancreatitis pain. Strategies targeting IL-6 actions through small molecule antagonists may offer novel approaches to improve therapy of chronic pancreatitis and other chronic pain states.

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“…Many studies also proved that the increased IL-6 gene expression enhanced NO production through increasing the induced iNOS expression (Kang et al 2007, Maalouf et al 2010. CRP has been suggested as a preferable biomarker for chronic and acute inflammation (Dortay et al 2011).…”

Section: Fig 4 Quantitative Rt-pcr Analysis Of Interleukin-1β (Il-1β)mentioning

confidence: 99%

Gene expression, oxidative stress and apoptotic changes in rabbit ileum experimentally infected with Eimeria intestinalis

Abdel-Haleem¹,

Aboelhadid²,

Sakran³

et al. 2017

FOLIA PARASIT

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Abstract:Coccidiosis is a parasitic disease caused by protists (apicomplexans) of the genus Eimeria Schneider, 1875 and is considered to be the most important disease faced by rabbit breeders due to its high morbidity. In the present study, the antioxidant status and changes in apoptosis and in the expression of some genes were quantified in rabbits' ilea following infection with Eimeria intestinalis Cheissin, 1948. Rabbits, orally infected with 1 × 10 5 sporulated oocysts of E. intestinalis, started to shed oocysts in their faeces on 8 days post infection (dpi) and reached maximum excretion on 10 dpi, with approximately 5 million oocysts. This was accompanied by a significant decrease in the live body weight of infected rabbits. Also, malondialdehyde and nitric oxide were significantly increased while catalase and glutathione were significantly decreased in the ileum tissues of the infected rabbits. In addition, a significant increase was observed in the percentages of apoptotic cells in the ilea of the infected rabbits. Furthermore, interleukin-1β and interleukin-2 mRNA levels were significantly down-regulated and mRNA levels of interleukin-6, interferon gamma and inducible nitric oxide synthase were significantly up-regulated, while those of C-reactive protein remained unchanged. We conclude that infection with E. intestinalis induces oxidative stress, a significant increase in the percentage of apoptotic cells and a diverse and robust Th1 and Th1-related cytokine response in the ileum tissues.

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Novel role of IL-6/SIL-6R signaling in the expression of inducible nitric oxide synthase (iNOS) in murine B16, metastatic melanoma clone F10.9, cells

Cited by 16 publications

References 67 publications

A Leaf Methanolic Extract of Wercklea insignis Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Blocking the NF-κB Signaling Pathway in RAW 264.7 Macrophages

A Leaf Methanolic Extract of Wercklea insignis Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Blocking the NF-κB Signaling Pathway in RAW 264.7 Macrophages

Reversal of pancreatitis-induced pain by an orally available, small molecule interleukin-6 receptor antagonist

Gene expression, oxidative stress and apoptotic changes in rabbit ileum experimentally infected with Eimeria intestinalis

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