Specific targeting of the IL-23 receptor, using a novel small peptide noncompetitive antagonist, decreases the inflammatory response.

IL-23 is part of the IL-12 family of cytokines and is composed of the p19 subunit specific to IL-23 and the p40 subunit shared with IL-12. IL-23 specifically contributes to the inflammatory process of multiple chronic inflammatory autoimmune disorders, including psoriasis, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. So far, one antibody targeting the shared p40 subunit of IL-12 and IL-23, Ustekinumab, is approved clinically to treat psoriasis.

Syk is a novel target of arsenic trioxide (ATO) and is involved in the toxic effect of ATO in human neutrophils.

The anticancer dug arsenic trioxide (ATO) is known to be toxic for human mononuclear and neutrophil cell populations by a mechanism that needs to be further investigated. Due to the well-characterized role of Syk kinase in phagocytosis and because activation and involvement of Syk in response to ATO treatment has never been reported in any cells, we decided to determine whether or not Syk is involved in the mode of action of ATO. Human neutrophils were freshly isolated and incubated in vitro with ATO and the role of Syk was evaluated in different neutrophil functions.

IL-4R(alpha), a new member that associates with Syk kinase: implication in IL-4-induced human neutrophil functions.

Although Syk has been reported to be associated with IL-2R beta [corrected] and IL-15R alpha in some hematopoietic cells, its association has never been investigated in the IL-4/IL-4R system. In this study, we demonstrate for the first time that Syk is constitutively associated with IL-4R(alpha)in human polymorphonuclear neutrophils (PMNs) and that IL-4 stimulation increases the amount of Syk associated with IL-4R(alpha). Moreover, upon IL-4 treatment, a pool of Syk associated with IL-4R(alpha) is phosphorylated.

Interleukin (IL)-4 induces leukocyte infiltration in vivo by an indirect mechanism.

Interleukin (IL)-4 is a cytokine known mainly for its anti-inflammatory activity. Using the in vivo murine air pouch model, we found that IL-4 significantly increased the number of leukocytes after 9 hours of treatment, consisting mainly of neutrophil (60%) and monocytic (40%) cell populations. Using an antibody array, we found that the expression of several analytes (predominantly CCL2) was increased by IL-4 before the arrival of leukocytes.

Immune system: maturation of myeloid cells.

Human and animal cell lines are important laboratory tools that can be used for studying a variety of cell functions. Some cell lines are blocked at a certain step of maturation and can be used in order to study the mechanisms involved in cell maturation. Because such cell lines can be differentiated toward a more mature-like phenotype after the addition of agents, they can replace primary cells in large screening experiments preventing daily isolation.

Herpes simplex virus-1 up-regulates IL-15 gene expression in monocytic cells through the activation of protein tyrosine kinase and PKC zeta/lambda signaling pathways.

IL-15 plays a seminal role in innate immunity through enhancing the cytotoxic function as well as cytokine production by NK and T cells. We have previously shown that exposure of PBMC as well as monocytic cells to different viruses results in immediate up-regulation of IL-15 gene expression and subsequent NK cell activation as an innate immune response of those cells to these viruses. However, no signaling pathway involved in this up-regulation has been identified.

Interaction of monocytic cells with respiratory syncytial virus results in activation of NF-kappaB and PKC-alpha/beta leading to up-regulation of IL-15 gene expression.

Respiratory syncytial virus (RSV) is a major human respiratory pathogen, particularly for infants. RSV is also a powerful inducer of cytokines, one of which is IL-15, an important immunoregulatory cytokine. IL-15 plays a key role in NK and T cell development and differentiation and also regulates NK cell/macrophage interaction, as well as monocyte/macrophage and granulocyte function.

Induction of apoptosis by herpes simplex virus-1 in neonatal, but not adult, neutrophils.

We report a study on the effect of herpes simplex virus 1 (HSV-1) infection on apoptosis of neutrophils from both adults and neonates and present evidence showing that HSV-1 enhances apoptosis in neonatal, but not adult, neutrophils. HSV-1 enhanced the expression of both Fas and Fas ligand on the surface of neonatal neutrophils. Treatments with anti-Fas antibody and a Fas ligand inhibitor significantly reduced the induction of apoptosis by HSV-1.