Hck Tyrosine Kinase Regulates TLR4-Induced TNF and IL-6 Production via AP-1

Smolinska, Maria; Page, Theresa H.; Urbaniak, Ania M.; Mutch, Brenda E.; Horwood, Nicole J.

doi:10.4049/jimmunol.1100967

Cited by 84 publications

(69 citation statements)

References 51 publications

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“…LPS phosphorylates Ras and Raf-1, upstream-kinases of ERK, and, subsequently, this phosphorylation activates ERK [19,20]. The activation of ERK regulates the expression of TNF-α mRNA via the activator protein-1 transcription factor pathway [21][22][23][24]. Shishodia reported that cisplatin enhanced the phosphorylation of Ras in macrophages [25].…”

Section: Discussionmentioning

confidence: 99%

A Possible Mechanism of Cisplatin-Induced Tumor Necrosis Factor (TNF)-α Production in Murine Macrophages

Kim¹,

Yamamoto²,

Nakamura³

et al. 2013

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Cisplatin has been used for the treatment of various solid cancers or sarcomas; however, it can induce severe adverse effects. Among these adverse effects, nephrotoxicity, which has the potential to be a dose-limiting factor of this agent, develops due to the secretion of tumor necrosis factor-α (TNF-α) from macrophages; however, the precise mechanisms are still unclear. To elucidate possible mechanisms, we investigated the involvement of mitogen-activated protein kinases (MAPK) and reactive oxygen species (ROS) in cisplatin-induced TNF-α mRNA expression and protein production in the mouse macrophage-like cell line, RAW 264. Cisplatin (1 μM) significantly increased TNF-α mRNA expression and protein production. Extracellular-regulated kinase (ERK) and p38 MAPK, but not c-Jun N-terminal kinase (JNK), phosphorylation increased in response to cisplatin. Although an ERK inhibitor (PD98059) suppressed both cisplatin-induced TNF-α mRNA expression and its protein production, a p38 MAPK inhibitor (SB203580) decreased TNF-α protein production only. A JNK inhibitor (SP600125) had no effect on cisplatin-induced TNF-α mRNA expression. Furthermore, a scavenger of ROS, N,N'-dimethylthiourea, suppressed both ERK activation and TNF-α mRNA expression. These results suggest that the phosphorylation of ERK by ROS is involved in cisplatin-induced TNF-α mRNA expression and that the signaling pathway of p38 MAPK is related to TNF-α protein production.

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Section: Discussionmentioning

confidence: 99%

A Possible Mechanism of Cisplatin-Induced Tumor Necrosis Factor (TNF)-α Production in Murine Macrophages

Kim¹,

Yamamoto²,

Nakamura³

et al. 2013

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“…Currently, the complex interactions between Src and other pathways remain to be established. The crosstalk signaling mechanisms that link inflammatory cells with cancer cells, including SDF-1-CXCR4-Src and Src-IL-6 signaling axes, result in a cycle leading to cancer development and progression (41)(42)(43). In leukemia, SDF-1 has been found to induce 'inside-out' signaling, which involves CXCR4 and Lyn, leading to aberrant adhesive responses.…”

Section: Functions Of Src In Cancermentioning

confidence: 99%

“…In leukemia, SDF-1 has been found to induce 'inside-out' signaling, which involves CXCR4 and Lyn, leading to aberrant adhesive responses. Furthermore, previous studies have shown that Src and Hck, the Src family members, are involved in the production of IL-6 in osteoblasts and inflammatory macrophages (42,43).…”

Section: Functions Of Src In Cancermentioning

confidence: 99%

The importance of Src signaling in sarcoma

et al. 2015

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Abstract. Src is a tyrosine kinase that is of significance in tumor biology. The present review focuses on Src, its molecular structure, and role in cancer, in addition to its expression and function in sarcoma. In addition, the feasibility of Src as a potential drug target for the treatment of sarcoma is also discussed. Previous studies have suggested that Src has essential functions in cell proliferation, apoptosis, invasion, metastasis and the tumor microenvironment. Thus, it may be a potential target for cancer therapy. Src has been found to enhance proliferation, reduce apoptosis and promote metastasis in certain subtypes of sarcoma, including osteosarcoma, chondrosarcoma and Ewing's sarcoma. Furthermore, a number of novel effective therapeutic agents, such as SI-83, which target Src have been investigated in vitro and in vivo. Bosutinib and dasatinib, which inhibit Src, have been approved by the U.S. Food and Drug Administration for the treatment of chronic myelogenous leukemia. In addition, vandetanib is approved for the treatment of medullary thyroid cancer. Furthermore, the Src inhibitor, saracatinib, is currently in clinical trials for the treatment of a variety of solid tumors, including breast and lung cancers. Thus, Src is considered to be an important factor in sarcoma progression and may present a novel clinical therapeutic target. This review demonstrates the importance and clinical relevance of Src in sarcoma, and discusses a number of small molecular inhibitors of src kinase, such as dasatinib and sarcatinib, which are currently in clinical trials for the treatment of sarcoma patients.

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“…Thus, the microbiome of the esophagus might be managed with probiotics, antibiotics or NF-kB-specific host cell pathway inhibitors to prevent cancer or other disorders in this anatomical location. TLRs play a crucial role in the early innate immune response to invading pathogens and are involved in observing endogenous danger signals through the sensing of PAMPs, mainly via myeloid differentiation primary response gene 88 (MyD88) adaptor protein [84,85]. In general, most bacteria can provide a source of ligands for TLRs that may act as target cell membrane receptors [86].…”

Section: Gall Bladder Cancermentioning

confidence: 99%

Cancer and the microbiome: potential applications as new tumor biomarker

Khan

Gil-Bazo

Castiglia

et al. 2014

Expert Review of Anticancer Therapy

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Authors contributed equallyMicrobial communities that colonize in humans are collectively described as microbiome. According to conservative estimates, about 15% of all types of neoplasms are related to different infective agents. However, current knowledge is not sufficient to explain how the microbiome contributes to the growth and development of cancers. Large and thorough studies involving colonized, diverse and complex microbiome entities are required to identify microbiome as a potential cancer marker and to understand how the immune system is involved in response to pathogens. This article reviews the existing evidence supporting the enigmatic association of transformed microbiome with the development of cancer through the immunological modification. Ascertaining the connection between microbiome and immunological responses with risk of cancer may direct to explaining significant advances in the etiology of cancer, potentially disclosing a novel paradigm of research for the management and prevention of cancer.

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Hck Tyrosine Kinase Regulates TLR4-Induced TNF and IL-6 Production via AP-1

Cited by 84 publications

References 51 publications

A Possible Mechanism of Cisplatin-Induced Tumor Necrosis Factor (TNF)-α Production in Murine Macrophages

A Possible Mechanism of Cisplatin-Induced Tumor Necrosis Factor (TNF)-α Production in Murine Macrophages

The importance of Src signaling in sarcoma

Cancer and the microbiome: potential applications as new tumor biomarker

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