Peripheral analgesic activities of peptides related to α‐melanocyte stimulating hormone and interleukin‐1β<sup>193–195</sup>

Poole, Stephen; Bristow, Adrian; Lorenzetti, Berenice B.; Das, Rose E. Gaines; Smith, T.W.; Ferreira, Sérgio Henrique

doi:10.1111/j.1476-5381.1992.tb14361.x

Cited by 37 publications

(28 citation statements)

References 21 publications

(23 reference statements)

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“…The asterisk marks significant difference. (Ferreira et al, 1988;Poole et al, 1992). A first hint to a sensitization of thin afferent nerve fibers came from an enhancement of capsaicin-induced vasodilatation in rat skin in vitro because capsaicin as well as noxious heat activate the same ion channel in nociceptive neurons (Herbert and Holzer, 1994;Herbert et al, 1995;Tominaga et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

2000

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Proinflammatory cytokines contribute to the development of inflammatory and neuropathic pain and hyperalgesia in many in vivo models. The rat skin model was used to investigate the effects of proinflammatory cytokines on the basal and heatevoked release of calcitonin gene-related peptide from nociceptors in vitro. In contrast to the excitatory effects of cytokines observed in vivo, none of the cytokines tested evoked any calcitonin gene-related peptide (CGRP) release at normal skin temperature of 32°C. However, the cytokines IL-1␤, tumor necrosis factor (TNF)-␣, and IL-6 but not IL-8 induced a pronounced and transient sensitization of the heat-evoked CGRP release from nociceptors in vitro. This heat sensitization was dose dependent, with EC 50 for IL-1␤ of 2.7 ng/ml and for TNF-␣ of 3.1 ng/ml. The maximum IL-1␤ effect reached almost 600% of the heat-evoked release, and the maximum TNF-␣ effect induced a rise in CGRP release of 350%. In contrast to IL-1␤ and TNF-␣, IL-6 did not induce heat sensitization when applied alone but was only effective in the presence of soluble IL-6 receptor. This suggests a constitutive expression of signaling receptors for TNF and IL-1␤ and the signal transduction molecule gp130 but not IL-6 receptor or IL-8 receptor. Furthermore, the acute cytokine signaling observed in the present study was independent of transcriptional pathways because sensitization occurred on short latency in vitro and under conditions that excluded chemotactic accumulation of immune cells from blood vessels. Our results demonstrate that interleukins may play an important role in the initiation of heat hyperalgesia in inflammation and neuropathy.

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Section: Discussionmentioning

confidence: 99%

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

2000

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“…This small peptide shares the anti-inflammatory and antipyretic effects of ␣-MSH (1-13) (Richards and Lipton, 1984b;Hiltz and Lipton, 1989;Mugridge et al, 1991;Hiltz et al, 1992;Poole et al, 1992;Uehara et al, 1992;Watanabe et al, 1993;Ceriani et al, 1994b;Macaluso et al, 1994;Bhardwaj et al, 1996;Ichiyama et al, 1999c;Luger et al, 1999;Haddad et al, 2001;Mandrika et al, 2001). Furthermore, ␣-MSH (11-13) reduced NF-B translocation to the nucleus much as the full-length ␣-MSH Barcellini et al, 2000;Mandrika et al, 2001).…”

Section: A Receptor Subtypes Involved In the Antiinflammatory Effectmentioning

confidence: 99%

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

et al. 2004

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“…It is of interest that KPT, the L-enantiomer, is collinear with human IL1b [193][194][195] . Originally, KDPT was reported to attenuate the IL-1b-mediated hyperalgesic response in a rat-paw pressure test (21,22). KDPT, however, does not appear to act as a simple or uniform IL-1b antagonist because the peptide did not have antipyretic activity against IL-1b in the rabbit pyrogen test (21).…”

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confidence: 99%

KdPT, a Tripeptide Derivative of α-Melanocyte–Stimulating Hormone, Suppresses IL-1β–Mediated Cytokine Expression and Signaling in Human Sebocytes

Mastrofrancesco

Kokot

Eberlé

et al. 2010

The Journal of Immunology

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Acne is the most common inflammatory skin disease in which IL-1 plays a central role. Although α-melanocyte–stimulating hormone has immunomodulatory effects, its usefulness as an anti-inflammatory agent in acne is hampered owing to its lipid- and pigment-inducing effects via activation of melanocortin receptors (MC-Rs). We used the immortalized human sebocyte line SZ95 as an in vitro model to investigate the anti-inflammatory potential of KdPT, a tripeptide derivative of the C-terminal end of α-melanocyte–stimulating hormone. KdPT potently suppressed IL-1β–induced IL-6 and IL-8 expression. Mechanistically, KdPT decreased IL-1β–mediated IκBα degradation, reduced nuclear accumulation of p65, and attenuated DNA binding of NF-κB. Moreover, KdPT reduced IL-1β–mediated generation of intracellular reactive oxygen species, which contributed to IL-1β–mediated cytokine induction. KdPT also reduced cell surface binding of fluorochrome-labeled IL-1β in SZ95 sebocytes. Analysis of the crystal structure of the complex between IL-1β/IL-1R type I (IL-1RI), followed by computer modeling of KdPT and subsequent modeling of the peptide receptor complex with the crystal structure of IL-1RI via manual docking, further predicted that the tripeptide, through several H-bonds and one hydrophobic bond, interacts with the IL-1RI. Importantly, KdPT did not bind to MC-1Rs, as demonstrated by blocking experiments with a peptide analog of Agouti signaling protein and by binding assays using MC-1R–expressing B16 melanoma cells. Accordingly, KdPT failed to induce melanogenesis. Our data demonstrate a promising anti-inflammatory potential of KdPT and point toward novel future directions in the treatment of acne—as well as of various other IL-1–mediated inflammatory diseases—with this small molecule.

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Peripheral analgesic activities of peptides related to α‐melanocyte stimulating hormone and interleukin‐1β^193–195

Abstract: 1 The hyperalgesic effects of interleukin-ll (IL-1i) and prostaglandin E2 (PGE2) were measured in rats.2 Hyperalgesic responses to IL-ip were inhibited in a dose-dependent manner by a-melanocyte

Cited by 37 publications

References 21 publications

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

KdPT, a Tripeptide Derivative of α-Melanocyte–Stimulating Hormone, Suppresses IL-1β–Mediated Cytokine Expression and Signaling in Human Sebocytes

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Peripheral analgesic activities of peptides related to α‐melanocyte stimulating hormone and interleukin‐1β193–195

Abstract: 1 The hyperalgesic effects of interleukin-ll (IL-1i) and prostaglandin E2 (PGE2) were measured in rats.2 Hyperalgesic responses to IL-ip were inhibited in a dose-dependent manner by a-melanocyte

Cited by 37 publications

References 21 publications

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

KdPT, a Tripeptide Derivative of α-Melanocyte–Stimulating Hormone, Suppresses IL-1β–Mediated Cytokine Expression and Signaling in Human Sebocytes

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Peripheral analgesic activities of peptides related to α‐melanocyte stimulating hormone and interleukin‐1β^193–195