Methamphetamine (METH) is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2) in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1, IL-6, and KC-GRO) and Th2 (IL-2, IL-10, and IL-4) cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR) in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection. use of amphetamines, including METH, affects immune function with a significant suppression of IL-2 (Potula et al., 2010), but not IL-4 production by T-lymphocytes, as well as a suppression of B-lymphocyte proliferation; however, this occurred only at the highest amphetamine concentrations (Steinkellner et al., 2011; Kwack et al., 2014). Considerable evidence exists linking drug abuse to immune dysregulation and enhanced susceptibility to the progression of chronic infections, such as HIV-1(Ellis et al., 2003; Mantri et al., 2014). METH use is associated with high-risk sexual behavior and high rates of HIV acquisition and progression (Jamieson et al., 1997; Ellis et al., 2003). In this report, we have used the mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection to study the effects of METH on T cell immune responses. Although LCMV is a relatively simple virus, encoding only four gene products, it has proven to be one of the best experimental systems for analyzing cellular immune responses (Zhou et al., 2012). Several studies have reported that acute infections induce remarkably high levels of antiviral T cells, while protracted Rabbit Polyclonal to Synaptophysin or chronic infections are associated with both functional impairment and deletion of virus-specific CD8 T cells (Khanolkar et al., 2002). T cell exhaustion has a major role in failure to control chronic infection. Expression of inhibitory receptors, including PD-1, an inhibitory receptor of the CD28CCTLA-4 family are up regulated considerably in chronic viral infection (Barber et al., 2006). This along with the inability to sustain functional T cell responses contribute to exhaustion. CD4 Th cells are central orchestrators of the immune response and differentially activate diverse branches of innate and adaptive immunity to guide the SKI-606 appropriate response to an invading pathogen (Penaloza-MacMaster et al., 2014). CD4 Th1 immunity is critical to sustain residual CD8 T-cell activity to control infection during persistent infection and is characterized in CD4 T cells by the secretion of IFN-, TNF-, and IL-2 (Matloubian et al., 1994). So far no study has addressed the role of METH in the context of SKI-606 chronic viral infection to analyze the effects on T cell immune responses. In this report, we have systematically analyzed the classic responses of CD4 and CD8 T cells in secondary lymphoid organ namely spleen during chronic LCMV infection in mice that have been exposed to chronic METH and the peripheral responses by measuring the serum cytokines. Our findings indicate that METH administered in a s.c. route altered T cells responses with important consequences, in a chronic LCMV infection model. METH effects on CD4 and CD8 cell percentages were modest although the expression of important markers of LCMV infection and T cell exhaustion SKI-606 such as PD-1 was greatly increased. Many of the METH effects were more pronounced by day 14 but normalized as infection progressed up to 56 days. Serum cytokine analysis revealed reduction of IL-2 production at all time points in METH-exposed infected mice than without. The serum pro-inflammatory (TNF, IL12p70, IL1, IL-6, and KC-GRO) and Th2 (IL-2, IL-10, and IL-4) cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice, suggesting that METH modulates the migratory properties of T cells during infection thus affecting immune activation. We also found another interesting up regulation of epidermal growth factor receptor (EGFR) in METH exposed LCMV infected mice at later times of infection, suggesting that signaling through EGFR may enable to establish persistent infection. Materials and methods Mice Male.
Methamphetamine (METH) is a highly addictive psychostimulant that not only affects
Categories
- 34
- 5- Receptors
- A2A Receptors
- ACE
- Acetylcholinesterase
- Adenosine Deaminase
- Adenylyl Cyclase
- Adrenergic ??2 Receptors
- Alpha2 Adrenergic Receptors
- Annexin
- Antibiotics
- ATPase
- AXOR12 Receptor
- Ca2+ Ionophore
- Cannabinoid
- Cannabinoid (GPR55) Receptors
- CB2 Receptors
- CCK Receptors
- Cell Metabolism
- Cell Signaling
- Cholecystokinin2 Receptors
- CK1
- Corticotropin-Releasing Factor1 Receptors
- DHCR
- DMTases
- DNA Ligases
- DNA Methyltransferases
- Dopamine D1 Receptors
- Dopamine D3 Receptors
- Dopamine D4 Receptors
- Endothelin Receptors
- EP1-4 Receptors
- Epigenetics
- Exocytosis & Endocytosis
- Fatty Acid Synthase
- Flt Receptors
- GABAB Receptors
- GIP Receptor
- Glutamate (Kainate) Receptors
- Glutamate (Metabotropic) Group III Receptors
- Glutamate (NMDA) Receptors
- Glutamate Carboxypeptidase II
- Glycogen Phosphorylase
- Glycosyltransferase
- GnRH Receptors
- Heat Shock Protein 90
- hERG Channels
- Hormone-sensitive Lipase
- IKK
- Imidazoline Receptors
- IMPase
- Inositol Phosphatases
- Kisspeptin Receptor
- LTA4 Hydrolase
- M1 Receptors
- Matrixins
- Melastatin Receptors
- mGlu Group III Receptors
- mGlu5 Receptors
- Monoamine Oxidase
- Motilin Receptor
- My Blog
- Neutrophil Elastase
- Nicotinic (??4??2) Receptors
- NKCC Cotransporter
- NMU Receptors
- Nociceptin Receptors
- Non-Selective
- Non-selective 5-HT
- OP3 Receptors
- Opioid, ??-
- Orexin2 Receptors
- Other
- Other Oxygenases/Oxidases
- Other Transcription Factors
- p38 MAPK
- p53
- p56lck
- PAF Receptors
- PDPK1
- PKC
- PLA
- PPAR
- PPAR??
- Proteasome
- PTH Receptors
- Ras
- RNA Polymerase
- Serotonin (5-HT2B) Receptors
- Serotonin Transporters
- Sigma2 Receptors
- Sodium Channels
- Steroid Hormone Receptors
- Tachykinin NK1 Receptors
- Tachykinin NK2 Receptors
- Tachykinin, Non-Selective
- Telomerase
- Thyrotropin-Releasing Hormone Receptors
- Topoisomerase
- trpp
- Uncategorized
- USP
Recent Posts
- 2012) using the Phenotypic Characteristic Search for human strains with markers for resistance to Adamantane, Oseltamivir, or both drugs
- Tissue were homogenized into single-cell suspensions and put through red bloodstream cell lysis
- A phase I/II study investigated the safety and efficacy of concurrent local palliative RT and durvalumab (PD-L1 inhibitor) in 10 patients with unresectable or metastatic advanced solid tumors [136]
- We believe that this hypothesis-generating study could open new avenues for exploring oxidative stress as a potential pathogenetic and, hypothetically, therapeutic target for mitigating CLL strong class=”kwd-title” Keywords: Leukemia, Lymphocytic, Gilbert’s, Syndrome Gilbert’s syndrome (GS) is the most common inherited disorder of bilirubin glucuronidation
- Such costs aren’t simple for tertiary-care hospitals in growing countries sometimes, since these already are powered by minimal budget which switches into provision of fundamental medical services mostly, laboratory, radiology, pharmacy services, and bed space
Tags
a 67 kDa type I transmembrane glycoprotein present on myeloid progenitors
and differentiation. The protein kinase family is one of the largest families of proteins in eukaryotes
Apoptosis
bladder
brain
breast
cell cycle progression
cervix
CSP-B
Cyproterone acetate
EGFR) is the prototype member of the type 1 receptor tyrosine kinases. EGFR overexpression in tumors indicates poor prognosis and is observed in tumors of the head and neck
EM9
endometrium
erythrocytes
F3
Goat polyclonal to IgG H+L)
Goat polyclonal to IgG H+L)Biotin)
GRK4
GSK1904529A
Igf1
Mapkap1
monocytes andgranulocytes. CD33 is absent on lymphocytes
Mouse monoclonal to CD33.CT65 reacts with CD33 andtigen
Palomid 529
platelets
PTK) or serine/threonine
Rabbit Polyclonal to ARNT.
Rabbit polyclonal to BMPR2
Rabbit Polyclonal to CCBP2.
Rabbit Polyclonal to EDG4
Rabbit polyclonal to EIF4E.
Rabbit polyclonal to IL11RA
Rabbit polyclonal to LRRIQ3
Rabbit Polyclonal to MCM3 phospho-Thr722)
Rabbit Polyclonal to RBM34
SB 216763
SKI-606
SNX-5422
STK) kinase catalytic domains. Epidermal Growth factor receptor
stomach
stomach and in squamous cell carcinoma.
TNFSF8
TSHR
VEGFA
vulva