Paneth cells and the innate immune response

Wehkamp, Jan; Stange, Eduard F.

doi:10.1097/01.mog.0000245541.95408.86

Cited by 41 publications

(31 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the upper gastrointestinal tract, the subgroup of human ␤-defensins (hBDs) is supposed to be a critical component of both the innate and adaptive immune responses to Candida infections with distinct antifungal efficacies and mechanisms for hBD-2 and hBD-3 (12,20,43,44). The expression of these two hBDs is under the control of proinflammatory cytokines like IL-1␤, TNF-␣, and epidermal growth factor (EGF) receptor ligands that in turn activate downstream effectors, including the transcription factors NF-B or activator protein-1 (AP-1) (6,40,46,47). Besides this direct antimicrobial effect, hBDs can protect the gastrointestinal mucosa by chemotactic properties recruiting polymorphonuclear leukocytes (PMN) to the site of infection (7,46).…”

mentioning

confidence: 99%

IL-1β and ADAM17 are central regulators of β-defensin expression in Candida esophagitis

Pahl¹,

Brunke²,

Steubesand³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Candida albicans resides on epithelial surfaces as part of the physiological microflora. However, under certain conditions, it may cause life-threatening infections, including Candida sepsis. We have recently shown that human β-defensins (hBDs) hBD-2 and hBD-3 are upregulated in Candida esophagitis and that this antifungal host response is distinctly regulated by NF-κB and MAPK/activator protein-1 (AP-1) pathways. Here, we show that C. albicans induces hBD-2 through an autocrine IL-1β loop and that activation of the epidermal growth factor receptor (EGFR) by endogenous transforming growth factor-α (TGF-α) is a crucial event in the induction of hBD-3. To further dissect upstream signaling events, we investigated expression of the central sheddases for EGFR ligands ADAM10 and ADAM17 in the healthy and infected esophagus. Next, we used pharmaceutical inhibitors and small-interfering RNA-mediated knock down of ADAM10 and ADAM17 to reveal that ADAM17-induced shedding of TGF-α is a crucial step in the induction of hBD-3 expression in response to Candida infection. In conclusion, we describe for the first time an autocrine IL-1β loop responsible for the induction of hBD-2 expression and an ADAM17-TGF-α-EGFR-MAPK/AP-1 pathway leading to hBD-3 upregulation in the course of a Candida infection of the esophagus.

show abstract

mentioning

confidence: 99%

IL-1β and ADAM17 are central regulators of β-defensin expression in Candida esophagitis

Pahl¹,

Brunke²,

Steubesand³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…The integrity of the mucosal barrier is maintained by tight junctions occurring between adjacent epithelial cells and the relative impermeability of the apical villous epithelium which serves as an important function in the innate immune system. Complementing these are other cells such as Paneth cells which secrete antimicrobial substances such as, lysozymes, cysteinerich defensins, and IgA and goblet cells which secretes mucus [15,53] . These and other intrinsic defense mechanisms in the intestinal mucosa dilute, limit the adherence and invasion of commensal and pathogenic microorganisms and antigens.…”

Section: Crohn's Diseasementioning

confidence: 99%

Genetic risks and familial associations of small bowel carcinoma

Shenoy

2016

WJGO

View full text Add to dashboard Cite

“…As mentioned, the etiology of IBD is only partially known [Wehkamp and Stange, 2006], but participation of environmental factors and genetic susceptibility is accepted. Mesalazine or sulfasalazine formulations are the first-line drugs for induction and maintenance of remission in UC, although the role of these drugs in the induction and maintenance of medically induced remission of CD is limited.…”

Section: Therapies In Inflammatory Bowel Diseasementioning

confidence: 99%

Pharmacogenetics of Therapy in Inflammatory Bowel Disease Patients

Mendoza¹,

Lana

Dı́az-Rubio³

et al. 2007

CPG

View full text Add to dashboard Cite

Recent expansion of pharmacotherapy of inflammatory bowel diseases (IBD) reflects an increasing understanding of the mechanisms involved in its pathogenesis. Individual variation in response to drugs is a major problem in clinical practice and is associated with various host factors, including sex, age, diet, alcohol consumption, smoking habits and genetic background. The study of the genetic determinants influencing interindividual differences in drug responses is known as pharmacogenetics. A common disease as IBD may be caused by different groups of genes in different people, showing smaller genetic variation than IBD patients globally considered. The classification of individuals based on sets of susceptibility alleles will make treatment more predictable and effective. Pharmacogenetics in IBD is developing in two main directions. One involves the identification and design of novel drug targets by exploiting current knowledge of the structure and function of IBD susceptibility genes. Another thrust of IBD pharmacogenetic research is directed at understanding how genetic variation determines the response to and the side effects of existing therapeutic agents. Pharmacogenetics holds the promise that drugs might one day be adapted to each person's own genetic background and therefore be more efficacious and safe. Therapies of future should put emphasis on the epidemiological, molecular and genetic basis of disease with the application to clinical practice, underscoring the final goal of personalized medicine.In this review, we focused on the basis of pharmacogenetics, on the recent advances of the field in the main therapies involved in IBD (Azathioprine / 6-Mercaptopurine, 5-Aminosalicylates, Glucocorticoids, Methotrexate, Infliximab) and speculate on the future of pharmacogenetics.

show abstract

Paneth cells and the innate immune response

Abstract: It is conceivable that these recent findings together with a better understanding of underlying mechanisms involved in the regulation and biology of Paneth cells will open up new therapeutic avenues for preventing infection as well as for causally treating inflammatory bowel diseases.

Cited by 41 publications

References 64 publications

IL-1β and ADAM17 are central regulators of β-defensin expression in Candida esophagitis

IL-1β and ADAM17 are central regulators of β-defensin expression in Candida esophagitis

Genetic risks and familial associations of small bowel carcinoma

Pharmacogenetics of Therapy in Inflammatory Bowel Disease Patients

Contact Info

Product

Resources

About