Topical heat shock protein 70 prevents imiquimod-induced psoriasis-like inflammation in mice

Abstract

Psoriasis is a chronic inflammatory skin disease with systemic manifestations and potential genetic etiology. The newest treatments utilize antibodies against one of several cytokines known to underlie the inflammatory signaling molecules that produce the skin and systemic symptoms. However, these agents must be regularly injected, and they may compromise the normal responses of the immune system. Furthermore, they do not address the causes of the abnormal immunoregulatory responses of the disease because the etiology is not yet completely understood. In this short-term treatment study, the potential anti-inflammatory activity of an alfalfa-derived Hsp70-containing skin cream (aHsp70) was tested on imiquimod (IMQ)-induced psoriasis-like lesions in wild-type mice. Treatment of the mice with the aHsp70 skin cream simultaneously with the imiquimod application mitigated the induction of psoriatic-like lesions and correlated with altered expression of various skin cytokines.

Therapeutic Implications of Targeting Heat Shock Protein 70 by Immunization or Antibodies in Experimental Skin Inflammation

“…This demonstration extends previous reports of a therapeutic potential of targeting Hsp70 by topical approaches in the IMQ mouse model as well as by Hsp70 vaccination in animal models of different autoimmune diseases such as rheumatoid arthritis and lupus erythematosus ( 4 – 6 , 9 , 10 ). In fact, there is also some evidence from a randomized controlled trial in which intravenous administration of the endoplasmic reticulum Hsp70 family member binding immunoglobulin protein (BiP) to patients with rheumatoid arthritis was associated with clinical and biological improvements in the disease activity ( 23 ).…”

“…Recently, an equivocal role of Hsp70 has been demonstrated in the imiquimod (IMQ)-induced skin inflammation mouse model which has become the most widely used murine model for preclinical studies of psoriasis-like dermatitis ( 9 – 11 ). While one study showed that topical application of Hsp70 led to a reduction of skin lesions and inflammatory markers ( 10 ), another study described similar effects using a topical Hsp70 inhibitor ( 9 ). Here, we further defined the role of Hsp70 (using murine [m]-, human [h]-, or plant [p]-Hsp70) as a treatment target in the IMQ mouse model and related in vitro assays.…”

“…In this disease, increased expressions of Hsp and immune responses to these proteins have been described (7). Recently, an equivocal role of Hsp70 has been demonstrated in the imiquimod (IMQ)-induced skin inflammation mouse model which has become the most widely used murine model for preclinical studies of psoriasis-like dermatitis (9)(10)(11). While one study showed that topical application of Hsp70 led to a reduction of skin lesions and inflammatory markers (10), another study described similar effects using a topical Hsp70 inhibitor (9).…”

Heat shock proteins in the physiology and pathophysiology of epidermal keratinocytes

“…This cytokine in turn can activate expression of CXCL9/10 genes coding for chemokines attracting CD8(+) T cells (Jacquemin et al 2017). Importantly, it has been recently found that topical application of a cream containing high concentration of inducible HSPA derived from alfalfa plant ( Medicago sativa ) onto murine skin reduced skin inflammation in experimental psoriatic-like lesions induced by imiquimol (Seifarth et al 2018).…”

Increased Levels of Interleukin-17A Exosomes in Psoriasis

“…Although recent biologic agents targeting different pro-inflammatory cytokines have revolutionized the management of psoriasis, these agents do not address the causes of the abnormal immunoregulatory responses of the disease, because the aetiology is not yet completely understood. The 70-kDa heat shock proteins (HSP70) are known to be potent immunomodulators, and their anti-inflammatory activity has recently been investigated in a murine psoriasis-like model (9).…”