Disease relevance of Il16

• Interleukin 16 is up-regulated in Crohn's disease and participates in TNBS colitis in mice [1].
• Colonic mucosal IL-16 levels were elevated in Crohn's disease, suggesting a role for IL-16 in the pathophysiology of inflammatory bowel disease [1].
• RESULTS: Colonic IL-16 protein levels were increased in patients with Crohn's disease (P<0.05) but not ulcerative colitis [1].
• IL-16 as an anti-inflammatory cytokine in rheumatoid synovitis [2].
• Exogenous interleukin-16 inhibits antigen-induced airway hyper-reactivity, eosinophilia and Th2-type cytokine production in mice [3].

High impact information on Il16

• METHODS: IL-16 messenger RNA and protein levels in inflammatory bowel disease tissues were determined by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay [1].
• Interleukin 16 is a ligand for CD4, and this implies CD4 acts as a sentinel receptor that can switch CD4+ T cells between immune and inflammatory functions [4].
• GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes [5].
• Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor [6].
• Immunohistochemical analysis revealed the IL-16 expression in infiltrating cells and epithelial cells in the DTH footpads [7].

Biological context of Il16

• Chemotaxis experiments with IL-16 of murine and human origin, using murine splenocytes or human T lymphocytes as targets, showed cross-species stimulation of motility [8].
• Analysis of CD4(+) T cell proliferation in vivo using BrdU labeling similarly failed to identify a hyperproliferative phenotype in T cells lacking IL-16 [9].
• Stimulation with anti-CD3 mAb induced transiently greater thymidine incorporation in IL-16-deficient CD4(+) T cells than wild-type controls, but there was no difference in cell survival or in the CFSE dilution profiles [9].
• Finally, we describe the role of pro-IL-16 as a T lymphocyte cell cycle growth suppressor [10].
• The impact of IL-16 on T cell apoptosis is also discussed [10].

Anatomical context of Il16

• In this study, we investigated what factors produced during the sensitization phase are responsible for epithelial cell priming for IL-16 production [11].
• Infiltrating CD4(+) T cells are a feature of Crohn's disease; however, the role of IL-16 in intestinal inflammation is unknown [1].
• Pro-IL-16 regulation in activated murine CD4+ lymphocytes [9].
• IL-16 is a proinflammatory cytokine that signals via CD4, inducing chemotactic and immunomodulatory responses of CD4+ lymphocytes, monocytes, and eosinophils [8].
• This suggests that another receptor for interleukin-16 might be operative for Langerhans cells in the mouse epidermis [12].

Associations of Il16 with chemical compounds

• The relevance of the priming effect associated with sensitization for IL-16 production and storage was confirmed in vivo by serotonin airway challenge of OVA-sensitized mice, resulting in rapid secretion of IL-16 into BAL fluid [11].
• This suggests that the initial response to allergen (sensitization) results in synthesis but not secretion of IL-16 [11].
• Consistent with the microarray reports, pro-IL-16 mRNA levels fell within 4 h of activation, and this response is inhibited by cyclosporin A [9].
• Exposure of these cells to IL-16 induces expression of the immediate-early gene, c-fos, via a signaling pathway that involves tyrosine phosphorylation [13].
• IL-16 production was induced in the epidermis and dermis during the elicitation phase of the CHS response with trinitrochlorobenzene [14].

Enzymatic interactions of Il16

• Pro-IL-16 comprises a C-terminal cytokine domain and an N-terminal prodomain that are cleaved by caspase-3 [9].

Regulatory relationships of Il16

• Tumor necrosis factor-alpha-induced synthesis of interleukin-16 in airway epithelial cells: priming for serotonin stimulation [11].
• Using T cells from CCR5(null) mice, we determined that IL-16-induced migration was significantly greater in the presence of CCR5 [15].
• Pro-IL-16 expressed in transfected tumor cells was previously shown to translocate to the nucleus and to promote G(0)/G(1) arrest by stabilizing the cyclin-dependent kinase inhibitor p27(Kip1) [9].

Other interactions of Il16

• We determined that ovalbumin (OVA)-sensitized mice have an increase in systemic tumor necrosis factor-alpha levels, and that serum or BAL fluid stimulation of bronchial epithelial cells results in production of IL-16 that is subsequently secreted only following serotonin stimulation [11].
• The mechanism for IL-16 production was shown to be caspase-3-dependent, and serotonin-induced secretion of IL-16 required binding of the serotonin type 2 receptor [11].
• In the present study, we observed increased S-phase kinase-associated protein 2 mRNA expression in IL-16 null mice, but basal expression and activation-dependent regulation of p27(Kip1) were no different from wild-type mice [9].
• Firstly, it appears that thoracic lymph node cells isolated from in vivo IL-16-treated ovalbumin-challenged animals produce less IL-4 (77%) and IL-5 (85%) upon antigenic re-stimulation, when compared to vehicle-treated mice [3].
• CONCLUSION: The three cytokines IL-16, IL-17, and IL-18 were detected at the fetomaternal interface with a tissue specific, stage-dependent distribution [16].

Analytical, diagnostic and therapeutic context of Il16

• IL-16 is only present in the bronchoalveolar lavage (BAL) fluid following airway challenge with either allergen or vasoactive amine [11].
• Prior DNA microarray studies suggested that IL-16 mRNA levels decrease following T cell activation, a property unique among cytokines [9].
• Molecular cloning and sequence analysis of interleukin 16 from nonhuman primates and from the mouse [17].
• Exogenous CD8+ T cells, infused into CD8(-/-) mice immediately after femoral artery ligation, selectively homed to the ischemic hind limb and expressed IL-16 [18].
• Immunohistochemistry was performed and revealed IL-16 immunoreactivity particularly in airway epithelial cells but also in cellular infiltrates in OVA-challenged mice [19].

References