User:Kacinska/Interleukin 16

Interleukin 16 is a pro-inflammatory pleiotropic cytokine. It's precursor, pro-interleukin-16 is a protein that in humans is encoded by the IL16 gene. This gene was discovered in 1982 at Boston University by Dr. David Center and Dr. William Cruikshank.

Function
The cytokine encoded by this gene is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of this cytokine is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. The cytokine function is exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Two alternatively spliced transcript variants encoding distinct isoforms have been reported. Interleukin 16 (IL-16) is released by a variety of cells (including lymphocytes and some epithelial cells) that has been characterized as a chemoattractant for certain immune cells expressing the cell surface molecule CD4. IL-16 was originally described as a factor that could attract activated T cells in humans, it was previously called lymphocyte chemoattractant factor (LCF). Since then, this interleukin has been shown to recruit and activate many other cells expressing the CD4 molecule, including monocytes, eosinophils, and dendritic cells.

The structure of IL-16 was determined following its cloning in 1994. This cytokine is produced as a precursor peptide (pro-IL-16) that requires processing by an enzyme called caspase-3 to become active. CD4 is the cell signaling receptor for mature IL-16.

The CD4 molecule is its primary receptor, although the chemokine receptor CCR5 enhances IL-16 binding. IL-16 is chemotactic for T cells, eosinophils, mast cells, and monocytes. Among the CD4+ T cells subsets, IL-16 preferentially induces migration of Th1 and Foxp3+ regulatory T lymphocytes (Tregs). In addition, IL-16 promotes Th1 and inhibits Th2 responses through CD3/T cell receptor mediated modulation of cytokine activity, possibly contributing against Th2-cell mediated diseases such as allergic asthma.

Interactions
Interleukin 16 has been shown to interact with:


 * GRIN2A,
 * GRIN2D,
 * KCNJ10,
 * KCNJ15,
 * Kir2.1,
 * PPP1R12A, and
 * PPP1R12B.

Gene structure and expression
Interleukin-16 (IL-16) is located on chromosome 15 q26.1–q26.3 in humans and on chromosome 7 D2–D3 in mice. The IL-16 gene contains seven exons and six introns and encodes a large precursor protein, pro-IL-16, which is enzymatically processed to generate mature (secreted) IL-16 from the C-terminal of pro-IL-16. The gene is highly conservative, there is high gene sequence homology for both pro-IL-16 and mature IL-16 when the human is compared with mouse, rat, feline, or simian, greater than 84% for all species. The IL-16 promoter contains two CAAT-box-like motifs and multiple binding sites for GA-binding protein (GABP) and GATA-1, GATA-2, and GATA-3 transcription factors. Two of the motifs constitute a dyad symmetry element that complexes with GABPa and GABPb. Activation then occurs when the co-activator, CREB-binding protein/p300 (where CREB is Ca2þ/cAMP-response element-binding protein), binds to GABPa and induces the IL-16 gene promoter. The promoter lacks a TATA-box.

The IL-16 m RNA is constitutively expressed at high levels. Under nondisease conditions, IL-16 mRNA is limited almost exclusively to lymphatic tissue and circulating immune cells such as CD4 + and CD8 + T cells, eosinophils, mast cells, and dendritic cells, but synthesis is not restricted to these cell types only. Nonimmune cells must be induced to transcribe IL-16 message. During an inflammatory response, in situ IL-16 mRNA is also detected in other cell types, such as bronchial epithelial cells and fibroblasts.

Interaction with HIV
IL-16 has been shown to strongly suppress HIV-1 LTR-mediated transcription in T cells, monocytic cells and dendritic cells. IL-16 improves macrophage phagocytosis ability with the down-expression of IL-10 and up-expression of pro-inflammatory cytokines such as IL-1a and IL-6, hence increases the antimicrobial effect and inhibits HIV replication in macrophages.