Cytokines and growth factors influence hair growth in vitro. Possible implications for the pathogenesis and treatment of alopecia areata

Abstract

Factors that influence the growth of the anagen hair follicle or initiate the switch to a catagen growth pattern have so far not been definitely determined, but there is increasing evidence that cytokines and growth factors play an important role during these processes. Recently we detected an aberrant in situ expression pattern of cytokines of the Th1 type (IFN gamma, IL-2) plus IL-1 beta expression in untreated alopecia areata (AA), and a switch to high levels of IL-10 TGF-beta 1 expression after successful treatment with the contact allergen diphenylcyclopropenone (DCP). Hence the question arose as to whether cytokines are able to arrest hair growth and whether IL-10 or TGF beta 1 have the capacity to antagonize this process. Using whole-organ cultures of microdissected human hair follicles we studied the effect of a panel of cytokines and growth factors on hair growth and on the gross morphology of the hair follicles in vitro. IL-2, IL-10 and IFN-gamma had no effect in this regard, whereas TGF beta 1 partially inhibited hair growth and EGF, TNF alpha and IL-1 beta completely abrogated it. EGF and TNF alpha induced the formation of a club-like hair follicle, similar to catagen morphology of the hair bulb, whereas hair follicles grown in the presence of IL-1 beta or TGF beta 1 showed no particular morphological changes. We conclude that cytokines and growth factors are pivotal regulators of hair growth at least in vitro. IL-1 is suggested as playing an important role during the pathogenesis of AA. Possible mediators of therapeutic contact dermatitis (IL-10, TGF beta 1, TNF alpha, PGE2) are, at least in vitro, not able to antagonize the IL-1 beta-triggered hair growth inhibition. Therefore, we infer that these mediators rather "modulate' the immune response in AA.

Double-stranded RNA induces inflammation via the NF-κB pathway and inflammasome activation in the outer root sheath cells of hair follicles

“…Previous studies have described IL-1 as a crucial mediator inducing cessation of hair growth in vivo and in vitro suggesting IL-1 signaling system is involved in catagen development. Also genetic analysis showed the significant association of the IL-1 family to AA susceptibility and severity141516. In the current study, we provide evidence that human ORS cells contain the necessary elements to form NLRP3 inflammasomes and dsRNA upregulates inflammasome elements and induce IL-1β via NLRP3 inflammasome activation.…”

“…These findings suggest that AA is an autoinflammatory diseased linked to the hyperactivation of the innate immune system. However, as IL-1β is known to be a potent inhibitor of human hair growth in vitro and increased during catagen period in murine skin, the increased expression of IL-1β in AA lesion in our study cannot completely exclude the possibility of variations in the hair growth1416.…”

“…However, our understanding of the involvement of inflammasome activation in AA is limited, although several papers have described the clinical significance of the interleukin (IL)-1 family in AA susceptibility and severity141516. Previous report showed the increased expression of IL-1β in lesional skin of AA and suggested its role in hair growth cycle14. IL-1 is an active pro-inflammatory cytokine secreted upon the activation of inflammasomes.…”

Current and Potential Agents for the Treatment of Alopecia Areata>

“…The hair follicle normally represents one of the few "immune privileged" tissue compartments [21,40,41], and only solitary Langerhans cells and no MHC class I expression are detectable by immunohistochemistry on bulbar epithelium of normal anagen hair follicles [24,42,43]. Furthermore, the T H 3 cytokine TGF-ß 1 is expressed on murine hair follicles in mid and late There are various mechanisms by which the inflammatory infiltrate may affect the hair follicle; it is possible that cytokines are directly affecting the hair follicle, because IL-1α, IL-1ß and TNF-α inhibit hair growth in vitro and lead to morphological changes of the hair follicle similar to those observed in AA [46,47]. Moreover, immunohistochemical studies have demonstrated an expression of FasL and Granzyme B in the perifollicular infiltrates of AA [48], indicating that the induction of apoptosis in hair follicle keratinocytes involves FasL-Fas interaction and Granzyme B.…”

Wound healing protects against chemotherapy-induced alopecia in young rats via up-regulating interleukin-1β-mediated signaling

“…In the clinic, several studies have successfully treated chronic leg ulcers using epidermal equivalents derived from cells of anagen HF outer root sheath, taking advantage of their high proliferation potential (Fox et al, 2016; Jimenez et al, 2015; Limat et al, 1996; Martinez et al, 2016; Ortega-Zilic et al, 2010; Renner et al, 2009; Tausche et al, 2003). On the other hand, it has been known, for decades, that wounding the murine skin can induce the telogen to anagen transition (Hoffmann et al, 1996; Jiang et al, 2010). Additionally and remarkably, wounding the skin can also induce epidermal cells to assume a HF stem cell phenotype and produce HFs de novo , in a process termed wound induced hair follicle neogenesis (WIHN), in mice (Ito et al, 2007; Seifert et al, 2012) and possibly in humans (Sun et al, 2009).…”