Each of these two groups was sub-divided into two subgroups. ATO also manifest dysregulated Ca++ homeostasis. ATO induces Ca++-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca++ homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. study (Nayak et al., 2007; Pion et al., 2007). Similarly, in a zebrafish model, 2C10 ppb arsenic levels in water augmented the viral load by 50-fold and bacterial load by 17-fold suggesting the immunosuppressive Albiglutide effects of arsenic (Nayak et al., 2007). Lower respiratory tract infections and diarrhea are more common in arsenic-exposed human populations, particularly among children from Bangladesh and other countries where high levels of arsenic in drinking water have been reported (Mazumder et al., 2000; Raqib et al., 2009; Rahman et al., 2011; Smith et al., 2011). Increased mortality from pulmonary tuberculosios has been reported in Chile from drinking arsenic-contaminated water (Smith et al., 2011). The higher incidence of opportunistic infections, allergy and asthma in arsenic-exposed human populations likely results from failure to Albiglutide maintain an equilibrated Albiglutide immune response. In this regard, arsenic exposure has been shown to inhibit proliferative response of T cells and alters their cytokine secretion profiles (Biswas et al., 2008). Arsenic also reduces the proportion of T helper cell (CD4) relative to T cytotoxic cells (CD8) ratio (CD4/CD8) in exposed children (Soto-Pena et al., 2006). Pre-natal exposure to arsenic significantly reduces thymic function via oxidative stress and apoptosis (Ahmed et al., 2012) and alters DNA methylation (Kile et al., 2014), which collectively are thought to contribute to immunosuppression in childhood. Furthermore, impaired T cell functions have also been reported in experimental animals subjected to arsenic (Burchiel et al., 2009; Martin-Chouly et al., 2011). Cutaneous contact hypersensitivity response is impaired in mice exposed to arsenic (Patterson et al., 2004; Zhou et al., 2006), and chronic arsenic exposure of mice significantly decreases adhesion property and phagocytic activity of splenic macrophages Albiglutide (Bishayi and Sengupta, 2003). In addition to the deleterious effects of environmental arsenic, ATO is a food and drug administration (FDA) approved chemotherapeutic agent and is used for the treatment of promyelocytic leukemia (PML) (Lengfelder et al., 2012). ATO treatment of patients with multiple myeloma and colon cancer, as well as those with PML, has been reported to contribute to recurrent herpes simplex and herpes zoster virus infection (Tanvetyanon and Nand, 2004; Nouri et al., 2006; Yamakura et al., 2014; Cardenas et al., 2015). T cell mediated immunity is attenuated in these arsenic-treated cancer patients by induction of regulatory T cells (Tohyama et al., 2013). The precise molecular mechanism by which Albiglutide arsenic impairs immune functions is yet to be defined. We demonstrated earlier that treatment of murine macrophage, Raw 264.7 cells with ATO diminished phagocytic functions. These effects were suggested to involve the unfolded protein response (UPR) signaling as 4-phenylbutyric acid (PBA), a chemical chaperone alleviated markers of UPR signaling, including GRP78, p-eIF2, and CHOP, and afforded protection against ATO-mediated changes in these innate immune cells (Srivastava et al., 2013). ATF4 increases the expression of CHOP which is also a UPR transcriptional regulator that has been shown to play an important role in the pathogenesis and survival of mycobacterium in mouse macrophage cells (Lim et al., 2011). ATF4 plays key roles MADH3 in diverse biological and patho-biological processes such as bone formation (Wang et al., 2012), hepatic steatosis (Jo et al., 2012) and glutamine-regulated cancer cell survival/apoptosis (Qing et al., 2012). Recent evidence indicates that ATF4 also participates in signaling of the toll like receptors 4 (TLR4), which in turn regulates cytokine production (Woo et al., 2009). In this study we determined that ATF4 is a central target involved in dampening of immune reactions in arsenic revealed.