Histamine Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production in an Intercellular Adhesion Molecule-1- and B7.1-Dependent Manner

Abstract

Lipopolysaccharide (LPS) is recognized as a key molecule in the pathogenesis of Gram negative sepsis and septic shock. In the present study, we demonstrate that LPS (1-1000 pg/ml) concentration dependently up-regulated the expression of intercellular adhesion molecule (ICAM)-1, B7.1, and B7.2 on human monocytes using fluorescence-activated cell sorting analysis, and that tumor necrosis factor (TNF)-␣ production induced by LPS in peripheral blood mononuclear cells (PBMCs) was inhibited by the addition of antibodies against these adhesion molecules, suggesting the dependence of TNF-␣ production on cell-cell interaction through these adhesion molecules. Moreover, we found that histamine (10 Ϫ7 -10 Ϫ4 M) concentration dependently inhibited the expression of ICAM-1 and B7.1, but not B7.2 on monocytes induced by LPS. Histamine also inhibited the responses of TNF-␣ production induced by LPS. The modulatory effects of histamine on ICAM-1 and B7.1 expression and TNF-␣ production were all concentration dependently antagonized by famotidine but not by d-chlorpheniramine and thioperamide, and were mimicked by selective H2-receptor agonists but not by H1-, H3-, and H4-receptor agonists, indicating the involvement of H2-receptors in the histamine action. Dibutyryl cAMP down-regulated ICAM-1 and B7.1 expression on monocytes stimulated by LPS, suggesting the mediation by the cyclic adenosine monophosphate-protein kinase A pathway of H2-receptor activation. These results as a whole indicated that histamine via H2-receptor inhibited the LPS-induced TNF-␣ production through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS.

IgE and IL‐33−mediated triggering of human basophils inhibits TLR4−induced monocyte activation

“…As an example, in line with our observations, histamine via H2R, has been shown to inhibit the cytokine response to microbial products of monocytes [28,32] and dendritic cells [33]. Differentiation of monocytes into macrophages, on the other hand, induces the preferential expression of H1R over H2R [34], leading to increased production of IL-8 upon exposure to histamine [35].…”

Histamine Receptor 2 is Required to Suppress Innate Immune Responses to Bacterial Ligands in Patients with Inflammatory Bowel Disease

“…10,[20][21][22] Using a panel of TLR ligands, we demonstrate that histamine exerts a diminished suppressive effect on cells from patients with IBD, possibly due to the decreased number of H 2 R + monocytes. The decrease in H 2 R + monocytes is negatively correlated with T H 17 cells in peripheral blood, which parallels the animal model data where increased IL-17 + lymphocytes were found in the mucosa of animals treated with a H 2 R antagonist or animals receiving H 2 Rdeficient lymphocytes.…”

Intercellular Adhesion Molecule-1 Mediates Cellular Cross-Talk between Parenchymal and Immune Cells after Lipopolysaccharide Neutralization

“…The mechanism by which dibutyryl cAMP inhibits ICAM-1 may be due to inactivation of NF-B because the promoter region of the ICAM-1 genes contains binding sites for NF-B (49), and cAMP inhibits the activation of NF-B in a variety of human cells (26,50). In support of our results, Morichika et al (26) have recently demonstrated that dibutyryl cAMP in a concentration-dependent manner inhibited LPSinduced ICAM-1 expression on monocytes. These results indicate that the intracellular cAMP levels are a determinant of ICAM-1 expression.…”

“…One of the possible inflammatory responses that are associated with decreased cAMP levels is an increased expression of ICAM-1 (25,26). Further reasons to focus on ICAM-1 were the following: 1) ICAM-1 is found on both type I and type II alveolar epithelial cells (9,24,27); 2) LPS stimulation increases expression of ICAM-1 on type II cells in vitro (9,24,27); 3) the ligand for ICAM-1, i.e., Mac-1 (CD11a/CD18), is localized on leukocytes (28); and 4) ICAM-1 plays a central role in cell-cell contact-mediated immune responses (29) and the adherence of leukocytes to epithelial cells (27).…”