The Role of Human Defensins in Gastrointestinal Diseases

Jost Langhorst; Kyung-Eun Choi

Disclosures

Expert Rev Clin Immunol. 2011;7(6):779-787. 

In This Article

Defensins in UC

Expression of the inducible HBDs is significantly increased in areas of active inflammation in UC.[5,28,33] While in in vivo studies comparing UC with controls no difference in expression of HBD-1 mRNA was found,[5] independent groups provided evidence that HBD-2, evaluated by mucosal mRNA, is highly induced in inflamed mucosa in UC patients.[5,12,62] HBD-2 expression is even significantly greater in UC compared with both controls and colonic CD patients,[5] and a significant increase in levels of HBD-2 mRNA in UC was found in comparison to healthy controls. Compared to CD, unspecific colitis, diverticulitis and healthy controls, mucosal HBD-2 was particularly elevated in samples from patients with inflamed UC.[12] The expression of HBD-2 in inflamed tissue from UC patients is indeed significantly enhanced compared with controls.[9,49] Furthermore, HBD-2 was increased by LPS in IBD patients and controls, confirming that HBD-2 production is stimulated by bacterial products.[49] Thus, it can be hypothesized that HBD-2 is correlated to mucosal inflammation, especially in UC.

Similarly, the expression of HBD-3 is strongly correlated with HBD-2 and is exclusively raised predominantly in the state of active inflammation in UC and neither in noninflamed UC nor control samples.[12] HD-5 and -6 expression can be observed in UC and has been shown to be mediated by Paneth cell metaplasia.[63] In addition, proinflammatory cytokines and entero-invasive bacteria are highly concentrated in inflamed tissue.

However, Ramasundara recently noted that in UC, the AMP upregulation is part of comprehensible events in response to the inflammation rather than being an active contributor to disease pathogenesis.[2] Furthermore, the data from Aldhous et al. confirmed that there is a differential increase of colonic HBD-2 mRNA expression with inflammation in specific locations in both CD and UC.[49] These differences in results may be due to methodology; for instance, in the sigmoid colon they confirmed that HBD-2 mRNA expression is indeed higher in UC than CD.[49]

Interestingly enough, on the one hand defensin release may be suppressed by different pathogenic bacterial strains and on the other hand may be positively triggered by other bacteria – that is, some bacteria may contribute to the host defense whereas others oppose this protective function. According to Wehkamp et al., some probiotics, including E. coli Nissle 1917, lead to HBD-2 expression while a considerable number of more than 40 different E. coli strains with many known pathogenic strains did not.[28] In addition, in healthy individuals, the level of mucosal HBD-2 secretion into the feces can be enhanced in response to probiotics.[64] Altogether, there is a body of evidence for HBD-2 as marker for inflammation in UC; however, as it is induced by both proinflammatory as well as protecting bacteria, its absolute relevance is uncertain yet.

Similarly, it remains unclear to date whether the increased defensin expression is more a symptom of the disease or may be part of the pathogenesis in IBD, especially since the inducible defensins are triggered by both proinflammatory cytokines as well as protective bacteria.[28,64]

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