Cathelicidin deficiency predisposes to eczema herpeticum

Howell, Michael D.; Wollenberg, Andreas; Gallo, Richard L.; Flaig, Michael J.; Streib, Joanne E.; Wong, Cathy; Pavicic, Tatjana; Boguniewicz, Mark; Leung, Donald Y.M.

doi:10.1016/j.jaci.2005.12.1345

Cited by 240 publications

(177 citation statements)

References 19 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…Understanding the mechanism by which IL-4 and IL-13 inhibit HBD expression is important because these cytokines are increased in AD skin and lavage fluid of CF patients (13,26). Additionally, the increased expression of IL-4 and IL-13 in AD skin is thought to increase the propensity of these patients to recurrent bacterial and viral skin infections by reducing AMP expression (5,16,27). In this study, we found that STAT-1 activation was inhibited by IL-4 and IL-13.…”

Section: Effect Of Socs-1 and Socs-3 Is Regulated By Stat-6mentioning

confidence: 99%

IL-4 and IL-13 Negatively Regulate TNF-α- and IFN-γ-Induced β-Defensin Expression through STAT-6, Suppressor of Cytokine Signaling (SOCS)-1, and SOCS-3

Albanesi

Fairchild

Madonna

et al. 2007

The Journal of Immunology

181

160

View full text Add to dashboard Cite

Human β-defensins (HBDs) are a major class of antimicrobial peptides that play an important role in the innate immune response, however, the induction and regulation of these antimicrobial peptides is not well understood. We demonstrate here that stimulation of keratinocytes with TNF-α/IFN-γ induces HBD-2 and HBD-3 by activating STAT-1 and NF-κB signaling. We further demonstrate that IL-4 and IL-13 activate STAT-6 and induce the suppressors of cytokine signaling (SOCS)-1 and -3. This interferes with STAT-1 and NF-κB signaling, thereby inhibiting TNF-α/IFN-γ-mediated induction of HBD-2 and HBD-3. These data suggest that targeting the STAT-1-signaling pathway or suppressor of cytokine signaling expression enhances β-defensin expression and represents a new therapeutic strategy for reduction of infection in human diseases associated with β-defensin deficiency.

show abstract

Section: Effect Of Socs-1 and Socs-3 Is Regulated By Stat-6mentioning

confidence: 99%

IL-4 and IL-13 Negatively Regulate TNF-α- and IFN-γ-Induced β-Defensin Expression through STAT-6, Suppressor of Cytokine Signaling (SOCS)-1, and SOCS-3

Albanesi

Fairchild

Madonna

et al. 2007

The Journal of Immunology

181

160

View full text Add to dashboard Cite

show abstract

“…115 As mentioned earlier, cathelicidin exhibits antiviral activity against HSV and vaccinia virus, and cathelicidin expression is inversely correlated with serum IgE levels in EH patients. 116 Skin from atopic patients with eczema herpeticum show reduced expression of cathelicidin, and cathelicidin deficient mice show higher levels of HSV-2 replication. 116 Human and mouse cathelicidin reduce vaccinia virus plaque formation in vitro, and CRAMP knockout mice show more vaccinia pox formation than in control mice.…”

Section: Viral Infectionsmentioning

confidence: 99%

Antimicrobial Peptides, Skin Infections, and Atopic Dermatitis

Hata

Gallo²

2008

Seminars in Cutaneous Medicine and Surgery

106

View full text Add to dashboard Cite

The innate immune system evolved over 2 billion years ago to first recognize pathogens then eradicate them. Several distinct defects in this ancient but rapidly responsive element of human immune defense account for the increased incidence of skin infections in atopics. These defects include abnormalities in the physical barrier of the epidermis, alterations in microbial pattern recognition receptors such as toll receptors and NOD, and a diminished capacity to increase the expression of antimicrobial peptides during inflammation. Several antimicrobial peptides are affected including; cathelicidin, HBD-2, and HBD-3, which are lower in lesional skin of atopics compared to other inflammatory skin diseases, and dermcidin, which is decreased in sweat. Other defects in the immune defense barrier of atopics include a relative deficiency in plasmacytoid dendritic cells. In the future, understanding the cause of these defects may allow therapeutic intervention to reduce the incidence of infection in atopic individuals and potentially decrease the severity of this disorder.

show abstract

“…This finding suggests a role for SNP rs6509541 via Siglec-8 in allergic diseases because tIgE is a useful marker for assessing allergic diseases. 35 Given that Siglec-8 is a key molecule involved in facilitating eosinophil apoptosis and that mutations in Siglec-8 may also be involved in other allergic and eosinophilic disorders, we investigated whether Siglec-8 SNPs are associated with other human eosinophilic disorders like EE. We selected eight SNPs encompassing the Siglec-8 gene with a coverage of 2 kb/SNP, including those associated with asthma.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma

et al. 2010

View full text Add to dashboard Cite

Sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) promotes the apoptosis of eosinophils and inhibits FceRI-dependent mediator release from mast cells. We investigated the genetic association between sequence variants in Siglec-8 and diagnosis of asthma, total levels of serum IgE (tIgE), and diagnosis of eosinophilic esophagitis (EE) in diverse populations. The effect of sequence variants on Siglec-8 glycan ligand-binding activity was also examined. Significant association with asthma was observed for SNP rs36498 (odds ratios (OR), 0.69, P¼8.8Â10 À5 ) among African Americans and for SNP rs10409962 (Ser/Pro) in the Japanese population (OR, 0.69, P¼0.019). Supporting this finding, we observed association between SNP rs36498 and current asthma among Brazilian families (P¼0.013). Significant association with tIgE was observed for SNP rs6509541 among African Americans (P¼0.016), and replicated among the Brazilian families (P¼0.02). In contrast, no association was observed with EE in Caucasians. By using a synthetic polymer decorated with 6¢-sulfo-sLe x , a known Siglec-8 glycan ligand, we did not find any differences between the ligand-binding activity of HEK293 cells stably transfected with the rs10409962 risk allele or the WT allele. However, our association results suggest that the Siglec8 gene may be a susceptibility locus for asthma.

show abstract

Cathelicidin deficiency predisposes to eczema herpeticum

Cited by 240 publications

References 19 publications

IL-4 and IL-13 Negatively Regulate TNF-α- and IFN-γ-Induced β-Defensin Expression through STAT-6, Suppressor of Cytokine Signaling (SOCS)-1, and SOCS-3

IL-4 and IL-13 Negatively Regulate TNF-α- and IFN-γ-Induced β-Defensin Expression through STAT-6, Suppressor of Cytokine Signaling (SOCS)-1, and SOCS-3

Antimicrobial Peptides, Skin Infections, and Atopic Dermatitis

Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma

Contact Info

Product

Resources

About