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Differential regulation of basal expression of inflammatory genes by NF-κB family subunits

Cellular & Molecular Immunology volume 16, pages 720–723 (2019)Cite this article

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The nuclear factor kappaB (NF-κB) family of transcription factors regulates immune and inflammatory responses and controls cell survival, proliferation, differentiation, and apoptosis.1 The five subunits of the NF-κB family, (RelA, RelB, c-Rel, p105/p50, and p100/p52), are categorized as activating (RelA, RelB, and c-Rel), or inhibitory (p105/p50 and p100/p52), based on the presence or absence of the transactivation domain and form homo- and heterodimers. Stimulus-dependent activation of NF-κB, either by the classical pathway involving the degradation of the inhibitor of NF-κB (IκB) or by the alternative pathway involving the partial degradation of p100 to p52 and formation of the p52/RelB dimer, has emerged as a central theme in the regulation of NF-κB-dependent genes.2,3,4 However, in Sertoli cells and some neurons, lymphocytes, and malignant cells, NF-κB has been shown to be constitutively active in the nucleus5,6 (www.bu.edu/nf-kb). Moreover, several recent studies have also identified disease-associated mutations in the NF-κB subunits that affect their expression level and transcriptional activity.2,7 Our understanding of the ways in which the changes in the basal level of NF-κB affect the subsequent basal regulation of the expression of NF-κB-dependent genes remain poorly defined.

In this study, we conducted a preliminary exploration of the role that each NF-κB subunit plays in the constitutive or basal expression of selected NF-κB-dependent genes. We examined the expression levels of several genes associated with inflammation in wild-type mouse embryonic fibroblast cells (MEFs), which act as sentinel cells in the inflammatory response,8 and compared these levels to those in knockout cells for each NF-κB subunit. We assessed the relative mRNA abundance to represent the actual amount of each gene transcript present in unstimulated cells. We summarized our findings for use as a basis for further understanding NF-κB-mediated inflammatory pathologies9 and targeted future investigations of NF-κB-dependent transcriptional regulation.

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Acknowledgements

We thank Dr. Denis Guttridge at The Ohio State University College of Medicine for the gift of the RelA and RelB knockout MEF cells. We thank Ms Erin O’Kelly for proofreading the article. This work was supported by the National Institutes of Health, NIH/NIAID grants R01AI116730 and R21AI144264 to P.R. and T.J.D. were supported by a Dermatology T32 predoctoral fellowship from the National Institutes of Health, NIH/NIAMS grant 5T32AR007569.

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  1. These authors contributed equally: Tristan J. de Jesús, Joshua T. Centore

Authors and Affiliations

  1. Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA

    Tristan J. de Jesús, Joshua T. Centore & Parameswaran Ramakrishnan

  2. Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA

    Parameswaran Ramakrishnan

  3. The Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA

    Parameswaran Ramakrishnan

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  1. Tristan J. de Jesús
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Contributions

T.J.D. planned and performed the experiments, analyzed and interpreted the data, and wrote the manuscript. J.T.C. performed the experiments and analyzed and interpreted the data. P.R. conceived the project, planned the experiments, analyzed the data, and edited the manuscript.

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Correspondence to Parameswaran Ramakrishnan.

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de Jesús, T.J., Centore, J.T. & Ramakrishnan, P. Differential regulation of basal expression of inflammatory genes by NF-κB family subunits. Cell Mol Immunol 16, 720–723 (2019). https://doi.org/10.1038/s41423-019-0242-0

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