Rabbit Anti-Human ARG1 Polyclonal antibody

Nitric oxide (NO) has emerged as an important regulator of upper airway inflammation, mainly as part of the local naso-sinusal defense mechanisms. Increased arginase activity can reduce NO levels by decreasing the availability of its precursor, L-arginine. Chronic rhinosinusitis (CRS) has been associated with low levels of nasal nitric oxide (nNO). Thus, the present study investigates the activity of arginase I (ARG1) and II (ARG2) in CRS and its possible involvement in the pathogenesis of this disease. Under endoscopic view, tissue samples of pathologic (n = 36) and normal (n = 29) rhinosinusal mucosa were collected. Arginase I and II mRNA levels were measured using real-time PCR. Our results showed low arginase I activity in all samples. The levels of ARG2 were significantly higher in patients with chronic rhinosinusitis compared to the control group (fold regulation (FR) 2.22 +/- 0.42 vs. 1.31 +/- 0.21, p = 0.016). Increased ARG2 expression was found in patients with CRS without nasal polyposis (FR 3.14 +/- 1.16 vs. 1.31 +/- 0.21, p = 0.0175), in non-allergic CRS (FR 2.55 +/- 0.52 vs. 1.31 +/- 0.21, p = 0.005), and non-asthmatic CRS (FR 2.42 +/- 0.57 vs. 1.31 +/- 0.21, p = 0.028). These findings suggest that the upregulation of ARG2 may play a role in the pathology of a distinctive phenotype of CRS.

CREB and C/EBP beta signaling pathways are modulated during inflammation and also targeted by Bacillus anthracis edema toxin (ET), but how these factors individually and jointly contribute to changes in immune cell function is poorly understood. Using CRISPR/Cas9 gene editing, macrophage cell lines lacking CREB and isoforms of C/EBP beta were generated and analyzed for changes in responses to LPS, ET, and IL-4. Macrophages lacking C/EBP beta suppressed induction of IL-10 and Arg1, while IL-6 was increased in these cells following exposure to LPS. Examination of C/EBP beta isoforms indicated the 38 kDa isoform was necessary for the expression of IL-10 and Arg1. ChIP-Seq analysis of CREB and C/EBP beta binding to targets on the chromosome of human PBMC identified several regions where both factors overlapped in their binding, suggesting similar gene targeting or cooperative effects. Based on the ChIP-Seq data, a panel of previously unknown targets of CREB and C/EBP beta was identified and includes genes such as VNN2, GINS4, CTNNBL1, and SULF2. Isoforms of a transcriptional corepressor, transducin-like enhancer of Split (TLE), were also found to have CREB and C/EBP beta binding their promoter and were up regulated by ET. Finally, we explore a possible layer of C/EBP beta regulation by a protein complex consisting of adenomatous polyposis coli (APC) and PKA. Collectively, these data provide new insights into the role of CREB and C/EBP beta as immunosignaling regulators and targets of an important bacterial virulence factor.