Brief Report: First identification of H₄ histamine receptor in healthy salivary glands and in focal sialadenitis in Sjögren's syndrome

Abstract

Objective. The conventional H 1 and H 2 histamine receptors have >10,000-fold lower avidity for histamine than H 4 histamine receptor, which has been implicated in autoimmune diseases. This study was undertaken to compare H 4 histamine receptor levels in the salivary glands (SGs) of healthy controls with those in the SGs of patients with primary Sjögren's syndrome (SS).Methods. H 4 histamine receptor messenger RNA (mRNA) was analyzed using real-time quantitative polymerase chain reaction, and the receptor protein was examined using immunostaining.

H4 histamine receptors inhibit steroidogenesis and proliferation in Leydig cells

“…Although HRH4 shows preferential distribution in cells of immunological relevance, such as T-cells, dendritic cells, monocytes, mast cells, and neutrophils (Medina & Rivera 2010), accumulating evidence indicates its functional expression in a variety of nonimmume tissues and cells, including intestinal epithelium, spleen, lung, stomach, CNS, nerves of nasal mucosa, enteric neurons, salivary glands, and even cancer cells (Nguyen et al 2001, Connelly et al 2009, Lethbridge & Chazot 2010, Medina & Rivera 2010, Stegaev et al 2012, suggesting an extensive ]-thymidine during the last 16 h of this incubation, and the radioactivity incorporated into DNA was measured as described in 'Materials and methods' section. Each bar is the meanGS.E.M.…”

Overexpression of histamine H4 receptors in the kidney of diabetic rat

“…Another original contribution of our study is to provide an intra-nephron localization of the H putative distinct roles to the other histamine receptors in the body, the latter including exocrine and endocrine functions in salivary glands [44] and the GI tract [25], respectively.…”

Targeting Th2-typified immune responses to prevent immunopathology in rheumatic diseases: belittled therapeutic strategies?

“…Using different experimental arthritis models, they demonstrate that innate effector cells, such as neutrophils and monocytes (collagen antibody-induced arthritis model), and acquired effector cells, like Th17 cells (collagen-induced arthritis model), play critical roles. Previous studies using antagonists of the H 1 and H 2 receptors have not been successful in treating autoimmune diseases; however, these antagonists do not affect the H 4 R 13. These findings indicate new therapeutic opportunities in RA, but also many other rheumatic diseases associated with increases in histamine and (upregulated) expression of H 4 R, in particular given its restricted expression to immune cells 13…”

“…In addition, recently it was demonstrated that TLR-induced activation of neutrophils promotes histamine production via a PI3 kinase-dependent mechanism 23. Likewise, it has been shown that cell types such as dendritic cells contribute to increased histamine levels during inflammation, although these cells may induce lower levels 13. It is interesting that activation of cells through triggering of the H 4 R requires much lower levels of histamine than with the H 1–3 receptors (∼100–1000-fold) 13.…”

“…Likewise, it has been shown that cell types such as dendritic cells contribute to increased histamine levels during inflammation, although these cells may induce lower levels 13. It is interesting that activation of cells through triggering of the H 4 R requires much lower levels of histamine than with the H 1–3 receptors (∼100–1000-fold) 13. Collectively, the increased numbers of mast cells, enhanced levels of histamine and numerous triggers to activate these and other cells to release histamine suggest that new approaches targeting histamine-associated pathways, as indicated by Cowden et al ,12 and including inhibition of mast cell activation, hold promise in various rheumatic diseases.…”