Dans ce contexte et avec l’appui d’un réseau de partenaires académiques (Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC, EA 4331) et hospitaliers (CHU de Poitiers), Bioalternatives a entrepris depuis plus d’une dizaine d’années un vaste programme de recherche sur la thématique du psoriasis. Nos travaux visent notamment à mieux caractériser le rôle et les effets individuels ou combinatoires de cytokines à polarité Th1, Th17 et Th22 (ex : IL-17A, IL-22, IL-1alpha, OSM et TNF-alpha) dans le développement de l’inflammation cutanée et l’inhibition de la différenciation épidermique. C’est dans ce sens qu’aujourd’hui, Bioalternatives vous propose une gamme de modèles et tests de pharmacologie in vitro innovants dédiés spécifiquement à l’évaluation de l’efficacité (screening, profiling, preuve de concept) pharmacologique de vos produits (APIs, biosimilaires, formulations, dispositifs médicaux) :
- Réponse immunitaire (libération de cytokines à polarité Th17/Th22)
- Induction dans des kératinocytes (ou épidermes reconstruit) d’un profil de type psoriatique par des cytokines
- Production de chimiokines, peptides antimicrobiens et expression de marqueurs de différenciation épidermique
- Analyses de marqueurs spécifiques par immunoassays ou RT-qPCR
Parmi l’ensemble des tests standards proposés par Bioalternatives dans le domaine du psoriasis, voici quelques exemples :
Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis
/dans Psoriasis, Psoriasis /par GuillaumeAcute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 activated by proinflammatory cytokines.
Imiquimod-induced skin inflammation in mice is dependent on IL-1R1 and MyD88 signaling but independent of the NLRP3 inflammasome
/dans Psoriasis, Psoriasis /par GuillaumeThe pathogenesis of inflammatory skin diseases such as psoriasis involves the release of numerous proinflammatory cytokines, including members of the IL-1 family. Here we report overexpression of IL-1α, IL-1β, and IL-1 receptor antagonist mRNA, associated to expression of IL-23p19, IL-17A, and IL-22 in skin cells
Inhibition of keratinocyte differentiation by the synergistic effect of IL-17A, IL-22, IL-1α, TNFα and oncostatin M
/dans Inflammation, Inflammation, Psoriasis, Psoriasis /par GuillaumeThis study highlights the precise role of cytokines in the skin inflammatory response (psoriasis). IL-22 and OSM more specifically drive epidermal hyperplasia and differentiation loss while IL-1α, IL-17A and TNFα were more involved in the activation of innate immunity.
Contribution of IL22 to experimental skin inflammation
/dans Inflammation, Inflammation, Psoriasis, Psoriasis /par GuillaumeFocused on in vitro human models, we present the mechanisms of action of IL22 as well as its involvement in structure, metabolism, differentiation, chemotaxis, antibacterial activity, innate immunity, and tissue remodeling of epidermis.
Keratinocytes under fire of proinflammatory cytokines: Bonafide innate immune cells involved in the physiopathology of chronic atopic dermatitis and psoriasis
/dans Atopic dermatitis, Dermatite atopique, Psoriasis, Psoriasis /par GuillaumeSpecific cytokine environment deregulation plays a central role on skin morphology and innate immunity, moving towards specific pathologies and opening the way to new therapeutic strategies.
Skin inflammation induced by the synergistic action of IL17A, IL22, OSM, IL1α and TNFα recapitulates some features of psoriasis
/dans Psoriasis, Psoriasis /par GuillaumeOur results demonstrate the important potentiating activities of IL17A, IL22, oncostatin M, TNF-alpha, and IL1alpha on keratinocytes. This is particularly interesting in the context of psoriasis where these cytokines are overexpressed and could synergize to play an important role in upregulation of chemokines and antimicrobial peptides production.
Keratinocytes as targets for cytokines in skin inflammation
/dans Acné, Acne, Atopic dermatitis, Dermatite atopique, Dermatologie, Dermatology, Psoriasis, Psoriasis /par GuillaumeCurrent knowledge about the effects of different cytokine families on keratinocytes, and more particularly theirinvolvement in skin inflammation and in the development of inflammatory skin diseases such as psoriasis
Cytokine-induced CEACAM1 expression on keratinocytes is characteristic for psoriatic skin and contributes to a prolonged lifespan of neutrophils
/dans Psoriasis, Psoriasis /par GuillaumeThese results show that cytokine-induced cell-surface expression of CEACAM1 by keratinocytes in the context of a psoriatic environment might contribute to the persistence of neutrophils and thus to ongoing inflammation and the decreased propensity for skin infection, typical for patients with psoriasis.
A role for T cell-derived interleukin 22 in psoriatic skin inflammation
/dans Psoriasis, Psoriasis /par GuillaumeThis study indicate that interleukin 22 is a cytokine produced by skin-infiltrating lymphocytes that is potentially involved in initiation and/or maintenance of the pathogenesis of psoriasis.
OSM (Oncostatin M) secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation
/dans Psoriasis, Psoriasis /par GuillaumeThese results demonstrate that OSM and its receptor play an important role in cutaneous inflammatory responses in general and that the specific effects of OSM are associated with distinct inflammatory diseases depending on the cytokine environment.
Keratinocytes as targets for IL10-related cytokines : a putative role in psoriasis pathogenesis
/dans Psoriasis, Psoriasis /par GuillaumeIn this review, we discuss recent knowledge about the effects of cytokines of the IL-10 family on keratinocytes and their potential role in psoriasis, a cutaneous inflammatory disease.
IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes
/dans Inflammation, Inflammation, Psoriasis, Psoriasis /par GuillaumeIL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. IL-22 signals through a class II cytokine receptor composed of an IL-22-binding chain, IL-22RA1, and the IL-10RB subunit, which is shared with the IL-10R.