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. 1998 Dec;43(6):856–860. doi: 10.1136/gut.43.6.856

Role of NF-κB in immune and inflammatory responses in the gut

M NEURATH 1, C BECKER 1, K BARBULESCU 1
PMCID: PMC1727350  PMID: 9824616

Abstract

NF-κB is a pleiotropic transcription factor with key functions in the intestinal immune system. NF-κB family members control transcriptional activity of various promoters of proinflammatory cytokines, cell surface receptors, transcription factors, and adhesion molecules that are involved in intestinal inflammation. The perpetuated activation of NF-κB in patients with active inflammatory bowel disease suggests that regulation of NF-κB activity is a very attractive target for therapeutic intervention. Such strategies include antioxidants, proteasome inhibitors, inhibition of NF-κB by adenoviral IκBα expression vectors, and antisense DNA targeting of NF-κB. These approaches will hopefully permit the design of new treatment strategies for chronic intestinal inflammation. 



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Figure 1 .

Figure 1

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Members of the NF-κB/IκB families. After activation of the cells IκB is degraded and NF-κB can translocate to the nucleus. 


Figure 2 .

Figure 2

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NF-κB signal transduction pathways initiated by IL-1, TNF and IL-18. Whereas TNF activates NIK via TRADD and RIP/TRAF2, IL-1 and IL-18 use IRAK/TRAF6 to activate NIK. NIK in turn activates IKKα which causes phosphorylation of IκB. Next, IκB is ubiquitinated and degraded via the proteasome pathway. Finally, NF-κB translocates into the nucleus and binds to its target DNA sequences. 


Figure 3 .

Figure 3

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Targeting of the NF-κB activation pathway in intestinal inflammation. While alkylating agents and antioxidants may block protein kinases, antisense DNA can inhibit translation of p65. In addition, corticosteroids lead to blockade of p65 and adenoviral expression vectors could deliver genes whose products inactivate NF-κB. 


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