The direct cellular target of topically applied pimecrolimus may not be infiltrating lymphocytes

Fiorentino, David; Chen, Richard; Stewart, Dedra; Brown, Kirsty; Sundram, Uma

doi:10.1111/j.1365-2133.2010.10190.x

Cited by 8 publications

(4 citation statements)

References 30 publications

(76 reference statements)

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“…Calcineurin can dephosphorylate, and thus activate, nuclear factor of T cells (NFAT). The activated NFAT is then translocated into the nucleus, where it up-regulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of T cells [20]. There are a variety of known CIs, including cyclosporine A, pimecrolimus and tacrolimus.…”

Section: Discussionmentioning

confidence: 99%

Pimecrolimus increases the melanogenesis and migration of melanocytes in vitro

Chen

Tan

et al. 2017

Korean J Physiol Pharmacol

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Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro. This research aimed to study the ability of pimecrolimus on stimulating melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Results showed that pimecrolimus at the dosages of 1, 10, 102 nM were neither mitogenic nor cytotoxic to melanocytes. The addition of pimecrolimus at 10, 102 and 103 nM significantly increased intracellular tyrosinase activity, which was consistent with the elevated content of melanin content at the same concentrations. The peak effect was seen at 72 h in response to 102 nM pimecrolimus. Results of the wound scratch assay and Transwell assays indicate that pimecrolimus is effective in facilitating melanocyte migration on a collagen IV-coated surface. In addition, MITF protein yield reached the highest by pimecrolimus at 102 nM. In brief, pimecrolimus enhances melanin synthesis as well as promotes migration of melanocytes directly, possibly via their effects on MITF protein expression.

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Section: Discussionmentioning

confidence: 99%

Pimecrolimus increases the melanogenesis and migration of melanocytes in vitro

Chen

Tan

et al. 2017

Korean J Physiol Pharmacol

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“…In a model of 2,4-dinitrochlorobenzene (DNCB)-induced AD in NC/Nga mice, topical treatment with pimecrolimus reduced the expression of TSLP [ 276 ], which, as previously mentioned, is an IL-7-like cytokine highly expressed in KCs after stimuli [ 277 ]. In addition, pimecrolimus impaired the activation of NFAT2 in human KCs from the outer root sheath and some of the inner root sheath of the hair follicles [ 278 ].…”

Section: Pharmacological Therapy To Restore Keratinocytesmentioning

confidence: 99%

The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis

Gallegos-Alcalá

Jiménez

Cervantes‐García

et al. 2021

IJMS

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The keratinocyte (KC) is the main functional and structural component of the epidermis, the most external layer of the skin that is highly specialized in defense against external agents, prevention of leakage of body fluids and retention of internal water within the cells. Altered epidermal barrier and aberrant KC differentiation are involved in the pathophysiology of several skin diseases, such as atopic dermatitis (AD). AD is a chronic inflammatory disease characterized by cutaneous and systemic immune dysregulation and skin microbiota dysbiosis. Nevertheless, the pathological mechanisms of this complex disease remain largely unknown. In this review, we summarize current knowledge about the participation of the KC in different aspects of the AD. We provide an overview of the genetic predisposing and environmental factors, inflammatory molecules and signaling pathways of the KC that participate in the physiopathology of the AD. We also analyze the link among the KC, the microbiota and the inflammatory response underlying acute and chronic skin AD lesions.

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“…Downregulation of the high-affinity IgE receptor on Langerhans cells and inhibition of the release of inflammatory mediators from mast cells and basophils may also partly explain the effect of CIs when used topically [69]. Finally, recent evidence suggests that topical CIs may not act primarily by inhibiting the calcineurin/NFAT axis in lymphocytes in the skin but rather that they may instead act by decreasing NFAT2 activity in follicular keratinocytes [70]. These characteristics further support the topical use of CIs in the treatment of psoriasis.…”

Section: Topical Calcineurin Inhibitorsmentioning

confidence: 99%