Rabbit anti-Human Interleukin 34 polyclonal antibody

Background Colony-stimulating factor 1 (CSF-1) and interleukin (IL)-34 are important for the functions of myeloid lineage cells and are involved in several chronic inflammatory conditions associated with tissue degeneration. The aim of this study is to evaluate the expression of CSF-1 and IL-34 in gingival tissue and gingival fibroblasts (GF) from patients with periodontitis and controls. Methods Gingival biopsies were obtained from 19 periodontitis patients and 15 controls. Expression of CSF-1 and IL-34 in gingival tissue was assessed by western blot and localization by immunohistochemistry. Expression of CSF1 and IL34 mRNA in GF was analyzed by real-time polymerase chain reaction and protein expression visualized by immunofluorescence stainings. CSF-1 and IL-34 secretion from GF was evaluated in response to tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, Escherichia coli lipopolysaccharide (Ec-LPS) and Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) stimulation, using enzyme-linked immunosorbent assays. Results CSF-1 was increased in gingival tissue from periodontitis patients compared with controls (P < 0.05) whereas IL-34 expression was similar. In GF from a non-periodontitis donor, stimulation with either TNF-alpha, IL-1 beta, Ec-LPS, or Pg-LPS, increased the secretion of CSF-1 (P < 0.05) and Ec-LPS stimulation increased IL-34 (P < 0.05). CSF-1 and IL-34 were expressed and secreted constitutively from GF, with comparable levels in GF from periodontitis patients and controls. Inflammatory stimuli increased the secretion of CSF-1 and IL-34 with comparable levels measured from GF from periodontitis patients and controls (P < 0.05). Conclusion The expression of CSF-1 and IL-34 in gingival tissue and fibroblasts suggests involvement in myeloid cell functions during periodontal inflammation.

CSF-1 is broadly expressed and regulates macrophage and osteoclast development. The action and expression of IL-34, a novel CSF-1R ligand, were investigated in the mouse. As expected, huIL-34 stimulated macrophage proliferation via the huCSF-1R, equivalently to huCSF-1, but was much less active at stimulating mouse macrophage proliferation than huCSF-1. Like muCSF-1, muIL-34 and a muIL-34 isoform lacking Q81 stimulated mouse macrophage proliferation, CSF-1R tyrosine phosphorylation, and signaling and synergized with other cytokines to generate macrophages and osteoclasts from cultured progenitors. However, they respectively possessed twofold and fivefold lower affinities for the CSF-1R and correspondingly, lower activities than muCSF-1. Furthermore, muIL-34, when transgenically expressed in a CSF-1-dependent manner in vivo, rescued the bone, osteoclast, tissue macrophage, and fertility defects of Csf1(op/op) mice, suggesting similar regulation of CSF-1R-expressing cells by IL-34 and CSF-1. Whole-mount IL34 in situ hybridization and CSF-1 reporter expression revealed that IL34 mRNA was strongly expressed in the embryonic brain at E11.5, prior to the expression of Csf1 mRNA. QRT-PCR revealed that compared with Csf1 mRNA, IL34 mRNA levels were lower in pregnant uterus and in cultured osteoblasts, higher in most regions of the brain and heart, and not compensatorily increased in Csf1(op/op) mouse tissues. Thus, the different spatiotemporal expression of IL-34 and CSF-1 allows for complementary activation of the CSF-1R in developing and adult tissues. J. Leukoc. Biol. 88: 495-505; 2010.