Interleukin-17: a revisited study (original) (raw)

International journal of immunopathology and pharmacology

Cytokine is a term used for a large group of proteins that are produced by a variety of cells in the body and act to stimulate, or inhibit, the functions of the same cells that produce them (autocrime) or of other cell types (paracrime) (1-29). Interleukin-17 (IL-17), now known as IL-17 A, was originally cloned from T cell hybridoma and has been characterized as a proinflammatory cytokine produced by CD4+ CD4?RO+ memory T cells. According to the human genome sequencing and proteomics, five additional members, IL-17B, IL-l7C, IL-17D, IL-17Ea,ndIL-17F, have been identified and cloned. Some cognate receptors for the IL-17 family have been identified as IL-17R, IL-17RH 1, IL-17RL (receptor like), IL-17RD and IL-17RE(30-31). Altough it is believed that IL-17 is released by Th 1 or ThO cells but not by Th2 cells(32), It is interesting that there are some report demonstrated that TH2 CD4+ cell clone from patients with nickelallergic contact dermatitis also released IL-17 (33). The IL-17 family members are different in expressions and proinflammatory responses. IL-l7B mRNA is expressed at very high levels in the spinal cord and at lower and variable levels in the trachea, prostate, lung, small intestine, testes, adrenal, and pancreas. In situ analysis of mouse spinal cord, dorsal root ganglia, and brain demonstrated that IL-l7B mRNA is primarily expressed by the neurons. Immunohistochemical analysis of human spinal cord, dorsal root ganglia, cerebral cortex, cerebellum, and hippocampus demonstrated that IL-17B protein is primarily localized to the neuronal cell bodies and axons (34). IL-17BR was found exclusively in human kidney, pancreas, liver, brain, and intestines (35). IL-17B and IL-17C were cloned and are related to IL-17 A with approximately 27% amino acid identity. Fluorescence-activated cell sorter analysis shows that IL-17B and IL-17C bind and stimulate the monocytic cell line, THP-l, to release TNF-u and IL 1-13 (36). IL-17D is preferentially expressed in skeletal muscle, brain, adipose tissue, heart, lung, and pancreas. Treatment of endothelial cells with purified rIL-17D protein stimulated the production ofIL-6, IL-8, and GM-CSF. The increased expression ofIL-8 was found to be NF-K B-dependent. rIL-17D also demonstrated an inhibitory effect on hemopoiesis of myeloid progenitor cells in colony formation assays (37). IL-17E is a ligand for the recently identified protein termed EVI27/IL-17BR, or IL-17 receptor homolog 1 (lL-17Rh 1). Murine EVI27 was identified by its location at a common site of retroviral integration in BXH2 murine myeloid leukemias. IL-17Rh 1 shows highest level expression in kidney and moderate expression in multiple other