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Clarification of the Molecular Mechanisms That Negatively Regulate Inflammatory Responses

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Chronic Inflammation

Abstract

Inflammation is an important host defence mechanism to fight against invading microbial pathogens. However, an excess of these responses can damage normal tissues and may cause autoimmune or allergic diseases. To prevent the onset of these diseases, inflammatory responses should be tightly regulated by the negative regulatory system. Dysfunction of this negative regulatory system is suggested to be the cause of these diseases, but little is known about the details. Our research goal is to identify key regulators of inflammation-related signal transduction pathways, and to clarify the molecular mechanisms for regulating inflammatory responses. We recently found that LIM domain-containing proteins constitute a new family of negative regulators of inflammatory responses. In this review, we summarise a series of our studies about the role of PDLIM2 (PDZ and LIM-domain protein-2) and related LIM proteins in the negative regulation of inflammatory responses. These studies should contribute to the development of new therapeutic tools to control the exaggerated inflammation seen in certain human diseases.

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References

  • Amm I, Sommer T, Wolf DH (2013) Protein quality control and elimination of protein waste: The role of the ubiquitin-proteasome system. Biochem Biophys Acta 1843:182–196

    Article  PubMed  Google Scholar 

  • Gregersen PK, Olsson LM (2009) Recent advances in the genetics of autoimmune diseases. Annu Rev Immunol 27:363–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayden MS, Ghosh S (2004) Signaling to NF-κB. Genes Dev 18:2195–2224

    Article  CAS  PubMed  Google Scholar 

  • Kaisho T, Tanaka T (2008) Turning NF-κB and IRFs on and off in DCs. Trends Immunol 29:329–336

    Article  CAS  PubMed  Google Scholar 

  • Nakahira M, Tanaka T, Robson BE, Mizgerd JP, Grusby MJ (2007) Regulation of signal transducer and activator of transcription signaling by the tyrosine phosphatase PTP-BL. Immunity 26:163–176

    Article  CAS  PubMed  Google Scholar 

  • Ono R, Kaisho T, Tanaka T (2015) PDLIM1 inhibits NF-κB-mediated inflammatory signaling by sequestering the p65 subunit of NF-κB in the cytoplasm. Sci Rep 5:18327

    Google Scholar 

  • Tanaka T, Soriano MA, Grusby MJ (2005) SLIM is a nuclear ubiquitin E3 ligase that negatively regulates STAT signaling. Immunity 22:729–736

    Article  CAS  PubMed  Google Scholar 

  • Tanaka T, Grusby MJ, Kaisho T (2007) PDLIM2-mediated termination of transcription factor NF-κB activation by intranuclear sequestration and degradation of the p65 subunit. Nat Immunol 8:584–591

    Article  CAS  PubMed  Google Scholar 

  • Tanaka T, Yamamoto Y, Muromoto R, Ikeda O, Sekine Y, Grusby MJ, Kaisho T, Matsuda T (2011) PDLIM2 inhibits T Helper 17 cell development and granulomatous inflammation through degradation of STAT3. Sci Signal 4:ra85

    Article  PubMed  Google Scholar 

  • Tanaka T, Shibazaki A, Ono R, Kaisho T (2014) HSP70 mediates degradation of the p65 subunit of nuclear factor κB to inhibit inflammatory signaling. Sci Signal 7:ra119

    Article  PubMed  Google Scholar 

  • te Velthuis AJ, Bagowski CP (2007) PDZ and LIM domain-encoding genes: molecular interactions and their role in development. Sci World J 7:1470–1492

    Article  Google Scholar 

  • Wurster AL, Tanaka T, Grusby MJ (2000) The biology of Stat4 and Stat6. Oncogene 19:2577–2584

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Takashi Tanaka .

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Tanaka, T. (2016). Clarification of the Molecular Mechanisms That Negatively Regulate Inflammatory Responses. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_9

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