Visualisation of tissue kallikrein, kininogen and kinin receptors in human skin following trauma and in dermal diseases

Abstract

During dermal injury and inflammation the serine proteases kallikreins cleave endogenous, multifunctional substrates (kininogens) to form bradykinin and kallidin. The actions of kinins are mediated by preferential binding to constitutively expressed kinin-B2 receptors or inducible kinin-B1 receptors. A feature of the kinin-B1 receptors is that they show low levels of expression, but are distinctly upregulated following tissue injury and inflammation. Because recent evidence suggested that kinin-B1 receptors may perform a protective role during inflammation, we investigated the specific occurrence of the kallikrein-kinin components in skin biopsies obtained from normal skin, patients undergoing surgery, basalioma, lichenificated atopic eczema, and psoriasis. The tissue was immunolabelled in order to determine the localisation of tissue pro-kallikrein, kallikrein, kininogen and kinin receptors. The kinin components were visualised in normal, diseased and traumatised skin, except that no labelling was observed for kininogen in normal skin. Of the five types of tissue examined, upregulation of kinin-B1 receptors was observed only in skin biopsies obtained following surgery. In essence, the expression of

B1 and B2 kinin receptor participation in hyperproliferative and inflammatory skin processes in mice

“…In addition, the PCNA staining was more specific in the basal layer of the epidermis. Schremmer-Danninger et al demonstrated a specific immunolabelling for kinin B 2 receptors in basal keratinocytes in the epidermis of normal skin [9]. The fact that these sites are specifically confined in skin tissue and is associated with a high mitotic activity suggests that BK may play an important role in epidermal cell proliferation [25].…”

“…Moreover, low molecular weight kininogen mRNA increases and both kinin receptors are upregulated in psoriatic skin. Later, the same authors were able to localise kinin components in normal, traumatised (surgery), basalioma and lichenificated skin [9]. Also, we have previously showed that both kinin receptors seemed to be important in neurogenic cutaneous inflammatory responses [10].…”

Evaluation of the Potentials of Autologous Blood Injection for Healing in Diabetic Foot Ulcers

“…Also every phase is dependent on certain cells and cytokines. For example: coagulation depends on platelets plus PDGF & TGF-b, 10 inflammation depends on neutrophils, macrophages plus LIF & IL-6, 11,12 angiogenesis depends on platelets & monocytes plus VEGF, 13,14 fibroplasia depends on fibroblasts plus NO, 10,15 contraction depends on myofibroblasts plus EGF & TGF-b & other kinases [16][17][18] and epithelialization depends on keratinocytes plus KGF & FGF-7 & PDGF & EGF & TGF-b. 19,20 Exogenous application of such growth factors to stimulate normal as well as impaired healing was tried, [2][3][4][5]21 despite controversies regarding degradation by proteases activity of wound fluids.…”

Activation of the human keratinocyte B1 bradykinin receptor induces expression and secretion of metalloproteases 2 and 9 by transactivation of epidermal growth factor receptor

“…The BDKRB2 is preferentially stimulated by bradykinin whereas Lys‐des[Arg 9 ]‐bradykinin (LDBK) or des[Arg 9 ]‐bradykinin (DBK) activates BDKRB1. The kinin BDKRB1 is expressed in normal human epidermis and like BDKRB2 participates in keratinocyte differentiation . BDKRB1 is up‐regulated during inflammation and by cytokines such as tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐2 and IL‐4 or by its own ligand, LDBK .…”

“…BDKRB1 is up‐regulated during inflammation and by cytokines such as tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐2 and IL‐4 or by its own ligand, LDBK . In normal human skin, BDKRB1 expression is either latent or low, but is increased in biopsies of patients with some skin diseases or after surgery . Nevertheless, during either acute or chronic inflammation, values for BDKRB1 agonists have not been quantified in injured skin.…”