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    Tumor Necrosis Factor–α and Interleukin‐1α Decrease the Adherence ofStreptococcus pyogenesto Cultured Keratinocytes
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    Abstract:
    We hypothesized that the primary epidermal cytokines, tumor necrosis factor (TNF)—α and interleukin (IL)—1α, which are produced after skin injury, modulate bacterial adherence and the initiation of group A streptococcal skin infections. Streptococcus pyogenes binds preferentially to highly differentiated keratinocytes in vitro, simulating the superficial human skin infection, impetigo, and providing a model system for testing this hypothesis. Exposure of keratinocytes to 10 ng/mL TNF-α for 20 h decreased adherence to undifferentiated and differentiated keratinocytes by 33% and 38%, respectively. Treatment with 1 ng/mL IL-1α decreased adherence to undifferentiated and differentiated keratinocytes by 23% and 18%, respectively. Exposure to both cytokines simultaneously produced an additive 50% reduction in adherence. These data suggest that TNF-α and IL-1α may play a role in cutaneous host defense by impeding streptococcal adherence and decreasing its ability to form a nidus of infection in the skin.
    Keywords:
    Streptococcus Pyogenes
    Impetigo
    Interleukin 20
    Abstract To investigate the interleukin‐8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensi‐tizer (2,4‐dinitrofiuorobenzene, 3‐n‐penladecylcatechol); (ii) tolerogen (5‐methyl‐3‐n‐pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin‐8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin‐8. Intcrleukin‐8 gene expression was markedly increased upon in vitro stimulation after 1‐6 h with contact sensitizers, tolerogen and the irritant. In contrast, in‐terlcukin‐8 production was not detectable in unstimulatcd normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin‐8 is a response to nonspecific stimuli and may play a critical role in the early response to immuno‐genic or inflammatory signals in man.
    HaCaT
    Northern blot
    Human skin
    Interleukin 20
    The faucial carrying of Streptococcus pyogenes in patients presenting impetigo was determined as a risk factor for non-suppurative complications (acute glomerulonephritis). The fauces cultures of these patients revealed a S. pyogenes colonization of 65% and all the isolates were penicillin-sensitive. It was concluded that the high percent of faucial colonization made a systemic antimicrobial treatment necessary.
    Impetigo
    Streptococcus Pyogenes
    Acute glomerulonephritis
    Citations (2)
    Interleukin (IL)-38 is a member of the IL-1 cytokine family with reported anti-inflammatory activity. The highest constitutive IL-38 expression is detected in the skin, where it is mainly produced by differentiating keratinocytes. However, little data are available regarding its biological functions. In this study, we investigated the role of IL-38 in skin physiology. We demonstrate here that dermal fibroblasts and epithelial cells of skin appendages, such as eccrine sweat glands and sebaceous glands, also express IL-38. Next, using two- and three-dimensional cell cultures, we show that endogenous expression of IL-38 correlates with keratinocyte differentiation and its ectopic overexpression inhibits keratinocyte proliferation and enhances differentiation. Accordingly, immunohistochemical analysis revealed downregulation of IL-38 in skin pathologies characterized by keratinocyte hyperproliferation, such as psoriasis and basal or squamous cell carcinoma. Finally, intracellular IL-38 can shuttle between the nucleus and the cytoplasm and its overexpression modulates the activity of the transcription regulators YAP and ID1. Our results indicate that IL-38 can act independently from immune system activation and suggest that it may affect the epidermis directly by decreasing proliferation and promoting differentiation of keratinocytes. These data suggest an important role of keratinocyte-derived IL-38 in skin homeostasis and pathologies characterized by epidermal alterations.
    Epidermis (zoology)
    Interleukin 20
    Interleukin 22
    Citations (20)
    Streptococcus pyogenes (group A in the Lancefield classification) is one of the most common human pathogens. Although this ubiquitous organism is responsible for a wide array of illnesses, most attention has focused on its relation to acute pharyngitis, because of the frequency of that condition and its potential for inciting acute rheumatic fever. The recent resurgence of invasive group A streptococcal infections,1,2 however, is a reminder that the pathogen can cause a variety of skin and soft-tissue infections, some of which are severe and even life-threatening.Streptococcal PyodermaPyoderma, or impetigo, is a localized, purulent infection of the . . .
    Streptococcus Pyogenes
    Impetigo
    STREPTOCOCCAL INFECTIONS
    Group A
    Human pathogen
    Citations (1,011)