Richard Gallo

..Further, we discuss recent insights into the regulatory mechanisms that control antimicrobial protein expression. Finally, we consider how impaired antimicrobial protein expression and function can contribute to disease...

..This review highlights recent observations on the importance of innate immune systems and the relationship with the normal skin microflora to maintain healthy skin...

..In this issue Carretero et al. (2007) expand on these findings by demonstrating that expression of human cathelicidin alters multiple signaling pathways in a keratinocyte cell line and enhances wound re-epithelialization in ob/ob mice...

..AMPs have been shown to be important in such diverse functions as angiogenesis, wound healing, and chemotaxis. As our knowledge of AMP biology expands, the precise role and relevance of these peptides will be better elucidated...

..These observations suggest that endogenous components of the extracellular matrix can stimulate endothelia to trigger recognition of injury in the initial stages of the wound defense and repair response...

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..JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub...

..Thus, a single gene product encoding an important defense molecule alters structure and function in the topical environment to shift the balance of activity toward direct inhibition of microbial colonization...

..These observations illustrate the immune defense potential of keratinocytes acting directly through storage and processing of antimicrobial peptides...

..Moreover, Cnlp+/+ mice were protected from oral infections with C. rodentium inocula that infected the majority of Cnlp-/- mice. These results establish cathelicidin as an important component of innate antimicrobial defense in the colon...

..These results indicate that cathelicidin is secreted in mammary gland and human milk, has antimicrobial activity against both Gram-positive and Gram-negative bacteria, and can contribute to the anti-infectious properties of milk...

..In this study, the expression of human cathelicidin hCAP18/LL-37 was investigated in the intestinal mucosa from patients suffering from ulcerative colitis or Crohn's disease...

..The importance of the epithelial contribution to host immunity is evident, as alterations in antimicrobial peptide expression have been associated with various pathologic processes...

..This article discusses the possible molecular mechanisms for the pathogenesis of rosacea from current clinical observations and laboratory research...

..Thus, we demonstrate what we believe to be a previously unexpected role for vitamin D3 in innate immunity, enabling keratinocytes to recognize and respond to microbes and to protect wounds against infection...

..The ability of collagen gel culture to mimic better the in vivo dermal environment may be due in part to this influence on dermatan sulfate and dermatan sulfate proteoglycan synthesis...

..A GPPPQGGRPQ peptide binds gram-positive Propionibacterium acnes and considerably inhibits bacterial growth. The peptide exhibiting innate immunity may be applied for treatment of various P. acnes-associated human diseases...

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..This article reviews the latest advances in the knowledge of cathelicidin antimicrobial peptides, with particular emphasis on their role in defense against invasive bacterial infection and associations with human disease conditions...

..Current and future studies are likely to implicate the presence of antimicrobial peptides in several unexplained human inflammatory disorders and to provide novel therapeutic approaches to the treatment of disease...

..coli in contrast to wild-type mice. In vitro, human S100A15 displayed antimicrobial activity against E. coli. Our findings suggest that E. coli modulates S100A15 and IL-8 expression of keratinocytes by recognition through TLR4...

..In this article, we review important recent advances in understanding the biology of antimicrobial peptides and their role in normal immunity and human disease...

..HIF-1alpha control of myeloid cell activity in infected tissues could represent a novel therapeutic target for enhancing host defense...

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..This study was designed to characterize the role of the human cathelicidin LL-37 in fungal skin infections such as dermatophytosis and tinea versicolor...

..Poorly named, antimicrobial peptides are multifunctional pillars around which the innate and adaptive immune response has evolved...

..Taken together, these observations suggest that proteolytic processing may alter the balance between cathelicidin antimicrobial and host immunostimulatory functions...

..Thus, these data suggest that S. epidermidis-derived delta-toxin cooperates with the host-derived antimicrobial peptides in the innate immune system to reduce survival of an important human bacterial pathogen...

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..Ongoing and future studies are likely to implicate AMPs in several unexplained human inflammatory disorders and to provide novel therapeutic approaches for the treatment of these diseases...

..Moreover, this study furthers our understanding of antimicrobial peptides by showing that their wound repair properties can be independent of antimicrobial function...

..Adult animals also showed delayed skin wound healing. Loss of Neu5Gc in hominid ancestors approximately 2 to 3 million years ago likely had immediate and long-term consequences for human biology...

..As these dual functions are complementary to the LL-37 peptide released from the C-terminus of full-length hCAP18/LL-37, human cathelicidin represents an elegant multifunctional effector molecule for innate immune defense of the skin...

..These findings confirm the role of cathelicidin in skin inflammatory responses and suggest an explanation for the pathogenesis of rosacea by demonstrating that an exacerbated innate immune response can reproduce elements of this disease...

..Thus, these data suggest that the production of PSMgamma and PSMdelta by S. epidermidis can benefit cutaneous immune defense by selectively inhibiting the survival of skin pathogens while maintaining the normal skin microbiome...

..Recent insights into these processes have advanced the understanding of disease pathogenesis and provided new therapeutic options for a variety of skin diseases...

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..Thus, sweat represents a unique mode of delivery for potent innate immune effector molecules in the absence of inflammation...

..These results suggest that cathelicidin has anti-inflammatory activity in skin that may be mediated in part by inhibition of HA-mediated processes...

..These findings demonstrate that targeted gene transfer of a xenobiotic cathelicidin confers resistance against infection and suggests the benefit of duplication and divergence in the evolution of antimicrobial peptides...

..acnes-induced ear swelling and granulomatous inflammation. The obtained data highlight the potential of using lauric acid as an alternative treatment for antibiotic therapy of acne vulgaris...

..These observations demonstrate that the balance of proteolytic activity at an epithelial interface will control innate immune defense...

..These findings support the hypothesis that hyaluronan works through IL-1beta and the cryopyrin system to signal sterile inflammation...

..Furthermore, 1,25D3 suppressed Bcl-3 expression in vitro and in vivo. This study identified Bcl-3 as an important modulator of cutaneous innate immune responses and its possible therapeutic role in AD...

..These findings provide a further rationale against the indiscriminate use of antibiotics...

..epidermidis to activate TLR2 signaling and induce antimicrobial peptide expression, thus enabling the skin to mount an enhanced response to pathogens...

..Taken together, these results indicate that the release of histone H4 by holocrine secretion from the sebaceous gland may play an important role in innate immunity...

..These observations highlight the concept that development of vaccines targeting microbial products may represent an alternative strategy to conventional antibiotic therapy...

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..Thus, we demonstrate a previously unrecognized role of cathelicidin in NK cell antitumor function...

..Thus, these variables may further control the functions of antimicrobial peptides in the skin...

..This review focuses on describing the involvement of TLRs in the development of skin infections and inflammatory diseases, and highlights the potential application of TLR agonists or antagonists in these skin diseases...

..Furthermore, pimecrolimus inhibited nuclear translocation of NFAT and NF-kappaB in keratinocytes. These observations uncover a previously unreported function for pimecrolimus in cutaneous innate host defense...

..Antimicrobial peptides may therefore provide a compensatory innate defense mechanism during development of cellular immune response mechanisms in the newborn period...

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..acnes-stimulated cytokine release. Taken together, these data suggest that granulysin peptides may be useful as topical therapeutic agents, providing alternatives to current acne therapies...

..In addition, dermatan sulfate and FGF-7 stimulated growth of normal keratinocytes in culture. Thus, dermatan sulfate, the predominant glycosaminoglycan in skin, is the principle cofactor for FGF-7...

..Taken together, our results define a previously unknown mechanism for initiation of sterile inflammation that involves recognition of released hyaluronan fragments as an endogenous signal of tissue injury...

..Polymethylmethacrylate (PMMA) microspheres of different sizes recently have been manufactured for use as a filler substances in the skin and other organs...

..This expression represents a previously unknown immunologic response to papillomavirus infection and may represent an important step in the pathogenesis of this disorder...

..CONCLUSION: The presence of antimicrobial peptides in nails with activity against relevant nail pathogens may account for the ability of the nail unit to resist infection in the absence of direct access to the cellular immune system...

..Taken together, these findings demonstrate that LL-37/hCAP-18 is a multifunctional antimicrobial peptide with a central role in innate immunity by linking host defense and inflammation with angiogenesis and arteriogenesis...

..The current study demonstrates that Th2 cytokines enhance VV replication in AD skin by subverting the innate immune response against VV in a STAT-6-dependent manner...

..aureus. CONCLUSIONS: A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus...

..In addition, clinical E. coli strains that were more resistant to LL-37 caused more severe urinary tract infections than did susceptible strains. Thus, cathelicidin seems to be a key factor in mucosal immunity of the urinary tract...

..These results suggest that ACTH stimulates IL-18 expression in human keratinocytes, which provides an insight into the interaction between ACTH and inflammatory mediators...

..Endogenous antimicrobial peptides participate in the innate defense of skin against a variety of pathogens. The systemic expression of these peptides in normal-appearing skin of patients with infective cellulitis is unknown...

..Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period...

..These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection...

..Eczema herpeticum (ADEH) develops in a subset of patients with atopic dermatitis (AD) because of disseminated infection with herpes simplex virus (HSV)...

..Therapies targeting the vitamin D3 pathway and thereby cathelicidin may provide new treatment modalities in the management of infectious and inflammatory skin diseases...

..Therapies targeting control of cathelicidin and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases...

..The organizational philosophy is to encourage diverse participation, and maintain an eye towards gender issues, junior scientists, minorities, and individuals with physical limitations. ..

..Addressing the aims of this proposal will continue to provide insight into the pathogenesis of human infectious disease and offer additional novel alternatives to standard antimicrobial therapy. ..

..Addressing the aims of this proposal will continue to provide insight into the pathogenesis of human infectious disease and offer additional novel alternatives to standard antimicrobial therapy. ..

..This work will suggest novel approaches for fighting infectious disease of the skin. ..

..This proposal will study the molecular mechanisms of these actions, and advance understanding of the beneficial effects of the normal skin microflora. ..

..Addressing the aims of this proposal will continue to provide insight into the pathogenesis of human infectious disease and offer additional novel alternatives to standard antimicrobial therapy. ..

..This work will suggest novel approaches for fighting infectious disease of the skin. ..

..The GAG ligand(s) responsible for activation will be sought and gene expression profiles investigated. Successful completion of these aims will reveal fundamental events in wound repair and may suggest new approaches to wound therapy. ..

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..This proposal will study the molecular mechanisms of these actions, and advance understanding of the beneficial effects of the normal skin microflora. ..