Disease relevance of RETNLB

• In vivo, FIZZ1 may modulate the function of neurons innervating the bronchial tree, thereby altering the local tissue response to allergic pulmonary inflammation [1].
• Human RELMbeta is a mitogenic factor in lung cells and induced in hypoxia [2].
• The results suggest that human RELMbeta may contribute to hypoxic-induced pulmonary vascular remodeling processes or hypoxia related fibrotic lung disease [2].
• CCRG belongs to a new class of growth factors and may be important in the diagnosis and treatment of colon cancers [3].
• Of particular note was the rapid upregulation in both WT and SCID mice of the genes encoding YM1, FIZZ1, and Arg1, indicating a role for alternatively activated macrophages (AAMs) in pulmonary innate immunity [4].

High impact information on RETNLB

• RESULTS: Messenger RNA for RELMbeta is restricted to the undifferentiated, proliferating colonic epithelium [5].
• METHODS: The regulation of RELMbeta messenger RNA expression was determined in LS174T, Caco-2, and HT-29 cell lines in response to stimulation with interleukin 13 and lipopolysaccharide [5].
• Quantitative reverse-transcription polymerase chain reaction, immunoblots, and immunohistochemistry were used to examine the expression of RELMbeta in BALB/c and C.B17.SCID mice housed in conventional, germ-free, and gnotobiotic environments [5].
• FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family [1].
• Murine (m) FIZZ1 is the founding member of a new gene family including two other murine genes expressed, respectively, in intestinal crypt epithelium and white adipose tissue, and two related human genes [1].

Biological context of RETNLB

• Murine mXCP1, mXCP2 and mXCP3 genes map to murine chromosome 16 and mXCP4 is positioned on chromosome 8; the hXCP1 and hXCP2 genes are located at homologous regions of chromosomes 3 and 19 [6].
• Induction of FIZZ2 gene expression most likely occurs independent of a direct effect by these cytokines and may be due to indirect STAT6-driven mechanisms [7].
• The promoter region of FIZZ1 contains functional binding sites for STAT6 and C/EBP [7].
• Point mutations in the STAT6 or the C/EBP site led to loss of cytokine responsiveness indicating that IL-4-mediated induction of murine FIZZ1 is orchestrated by the coordinate action of STAT6 and C/EBP [7].
• Upon transfection of a RELMbeta encoding expression plasmid into these cells, we observed significant induction of proliferation particularly in SMC and A549 cells, which could be blocked by phosphatidyl-inositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin [2].

Anatomical context of RETNLB

• Both resistin and FIZZ1/RELMalpha are expressed in adipose tissue [8].
• In control mice, FIZZ1 mRNA and protein expression occur at low levels in a subset of bronchial epithelial cells and in non-neuronal cells adjacent to neurovascular bundles in the peribronchial stroma, and in the wall of the large and small bowel [1].
• FIZZ1, but not FIZZ2, mRNA was up-regulated upon incubation of the myeloid cell line BMnot with IL-4 [7].
• RELMbeta mRNA was upregulated in hypoxia in human lung A549 cell line as well as primary cultured adventitial fibroblasts and smooth muscle cells (SMC) of pulmonary arteries [2].
• Supernatant from COS cells transfected with the CCRG expression vector stimulated proliferation of colon cancer cells [3].

Associations of RETNLB with chemical compounds

• It is concluded that the expression of the genes encoding FIZZ1 and FIZZ2, but not FIZZ3, is induced in allergen-challenged lungs in a STAT6-dependent fashion [7].
• Besides the earlier documented markers, macrophage mannose receptor and arginase 1, we demonstrated recently that murine aaMF are characterized by increased expression of found in inflammatory zone 1 (FIZZ1) and the secretory lectin Ym [9].
• The rate of lactate production was found to be relatively uniform over a range of cataract severities which were determined from the CCRG classification [10].
• An interesting correlation was also observed between the degree of light scatter as determined by the 290-nm excitation peak for intrinsic lens tryptophan fluorescence and the CCRG (photographic) appearance of these cataractous lenses [11].

Other interactions of RETNLB

• Macrophages from CCR4(-/-) mice exhibited many features consistent with alternative activation, including elevated secretion of type 2 cytokines/chemokines and the found in inflammatory zone 1 (FIZZ1) protein [12].

Analytical, diagnostic and therapeutic context of RETNLB

• Bronchoalveolar lavage fluid from mice with experimentally induced allergic pulmonary inflammation contains a novel 9.4 kDa cysteine-rich secreted protein, FIZZ1 (found in inflammatory zone) [1].

References