Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light.

Köck, A; Schwarz, Thomas; Kirnbauer, Reinhard; Urbanski, Agatha; Perry, P; Ansel, John C.; Luger, Thomas A.

doi:10.1084/jem.172.6.1609

Cited by 658 publications

(358 citation statements)

References 30 publications

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“…We have recently shown that urocanic acid, which has been implicated as the photoreceptor within the skin for UV radiation and mediator of some immune suppressive effects of UVB, is not able to down-modulate CR expression in human neutrophils in vitro [36]. It is well established that UVB-irradiated keratinocytes secrete a wide variety of modulatory cytokines, of which tumor necrosis factor ␣ and interleukin-10 are perhaps the most important [37,38]. It is known that tumor necrosis factor ␣ is a stimulatory cytokine for phagocytes, capable of up-regulating, for instance, leukocyte CR3 [39].…”

Section: Discussionmentioning

confidence: 99%

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation

Leino

Saarinen

et al. 1999

Journal of Leukocyte Biology

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We examined systemic effects of wholebody UVB irradiation on human peripheral blood phagocytes. We found that 24 h after a single erythemal dose of UVB radiation two phagocyte functions, adhesion and phagocytosis, were reduced by 50%. This functional suppression was accompanied by a significant decrease in the expression of complement receptors (CR1 and CR3) and IgG Fc receptors (FcRII and FcRIII). The greatest reduction (47%) was observed in CR3, which is important for both adhesion and phagocytosis. A kinetic analysis showed that both CR1 and CR3 levels started to decrease 15 min after the UVB exposure, reaching the lowest levels at 4.5-and 24-h time points, respectively. The down-modulation of CRs after whole-body UVB exposure was not due to a defective receptor synthesis or translocation from internal stores to plasma membrane because the maximal CR levels in stimulated cells were not affected by UVB. No change in the serum soluble ICAM-1 was detected after UVB, which rules out CD11b epitope masking by sICAM-1. UVB did not release low-receptor-density myeloid progenitor cells from storage pools into circulation. Interleukin 10, a mediator of UVB-induced immunosuppression, was unable to modulate CR expression in vitro. When seven suberythemal whole-body UVB exposures were given repeatedly within 2 weeks, a significant decrease in CR expression was seen, which was greatest after three irradiations. Our data suggest that an exposure to UVB has systemic effects in humans which, possibly due to the down-modulation of preexisting cell-surface receptors, suppress some important functions of circulating phagocytic cells. J. Leukoc. Biol. 65: 573-582; 1999.

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Section: Discussionmentioning

confidence: 99%

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation

Leino

Saarinen

et al. 1999

Journal of Leukocyte Biology

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“…Lewis et al (15) found a large release of TNFa from keratinocytes in vitro in response to irritants. TNFa will also be released from keratinocytes in response to lipopolysaccharides (16). TNFa is proinflammatory and activates T cells, macrophages and granulocytes, inducing altered expression of cellular adhesion molecules and release of cytokines (17).…”

Section: Tnfa Irritancy and Allergymentioning

confidence: 99%

Contact allergy, irritancy and ‘danger’

2000

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Conventional models of the immune response are based on distinguishing self and non-self. However, we consider that the more recently proposed 'danger' model may be an illuminating alternative for studying allergic contact dermatitis. In this model, an antigenic signal on its own would tend to produce tolerance. In contrast, in the presence of a 'danger' signal, which, in the case of allergic contact dermatitis, we suggest is usually cutaneous irritancy, the immune system would become activated, leading first to the induction of sensitization and then subsequently to the elicitation of a contact hypersensitivity response. In most cases, both the antigenic signal and irritant signal will come from the hapten, although, e.g., in an occupational setting, traumiterative dermatitis would be the source of the 'danger' signal. Typically, the irritant signal tends to be more concentration-dependent and thus is the overriding factor in the determination of the effective sensitizing and eliciting concentrations of the hapten. A further prediction of this hypothesis is that successful experiments demonstrating low-dose tolerance with contact allergens may be explained by the loss of the irritant effect at lower dilutions, whilst an antigenic stimulus remains present.

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“…Following U.V.-induced skin inflammation in mice, keratinocytes secrete increased levels of ET-1 (Ahn et al, 1998). Keratinocytes also produce pro-inflammatory cytokines such as TNF-α, TGF-β and IL-1β that in turn, can trigger ET-1 synthesis and secretion from endothelial and epithelial cells (Ahn et al, 1998;Ansel et al, 1990;Kock et al, 1990). Human polymorphonuclear neutrophils (PMNs) also synthesize ET-1, providing an additional source to accompany inflammatory cytokine release in the early stages of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous endothelin-A receptors elevate post-incisional pain

Mujenda

Duarte

Reilly

et al. 2007

Pain

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The contribution of endothelin-1 (ET-1), acting via endothelin-A receptors (ET A ), on post-incisional pain was examined in a rat model of incision through the hairy skin of the lumbar dorsum. Postincisional mechanical hyperesthesia was evaluated by cutaneous trunci muscle reflexes (CTMR) of subcutaneous muscles responding to stimulation with von Frey filaments near the wound (primary responses) and at a distance, especially on the contralateral dorsum (secondary responses, involving spinal circuits). The role of ET A was determined by pre-incisional, subcutaneous injection of the selective receptor antagonist BQ-123 at the incision site, 15 min or 24 hr before surgery. Control incisions showed both primary tactile allodynia and hyperalgesia, and a weaker secondary hyperesthesia, peaking 3-4 h after surgery and lasting at least 24h. Primary allodynia, but not hyperalgesia, was dose-dependently suppressed by 15 min pre-incisional BQ-123. In contrast, both secondary allodynia and hyperalgesia were inhibited by local BQ-123. The suppression of primary allodynia by local antagonist disappeared in 24 h, but that of secondary hyperesthesia remained strong for at least 24 h. Systemically delivered BQ-123 was without effect on any post-incisional hyperesthesia, and if the antagonist was locally injected 24 h before surgery there was no difference on hyperesthesia compared to vehicle injected at that time. We conclude that ET-1, released from skin by incision, activates nociceptors to cause primary allodynia and to sensitize spinal circuits through central sensitization. Blockade of ET A in the immediate peri-operative period prevents the later development of central sensitization.

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Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light.

Cited by 658 publications

References 30 publications

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation

Contact allergy, irritancy and ‘danger’

Cutaneous endothelin-A receptors elevate post-incisional pain

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