Identification and Characterization of Poly(I:C)-induced Molecular Responses Attenuated by Nicotine in Mouse Macrophages

Cui, Wenyan; Zhao, Shufang; Polanowska-Grabowska, Renata; Ju, Wang; Wei, Junnian; Dash, Bhagirathi; Chang, Sulie L.; Saucerman, Jeffrey J.; Gu, Jun; Li, Ming D.

doi:10.1124/mol.112.081497

Cited by 37 publications

(31 citation statements)

References 69 publications

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“…Considering the highly immunocompromised microenvironment of PDAC, however, it is likely that more potent M1 agonists may be required to restore immune surveillance. Several macrophage-activating immunotherapies are in clinical trials for the treatment of a variety of malignancies, including blocking antibodies to colony stimulating factor–1 (CSF-1) (42); TLR-activating agents PAM3CSK4 (43) and Poly I:C (44); and blocking antibodies to IL10 (45). It is possible that coupling such agents to albumin nanoparticles may improve their delivery to macrophages in the tumor microenvironment and more efficiently restore immune recognition.…”

Section: Discussionmentioning

confidence: 99%

Macropinocytosis of Nab-paclitaxel Drives Macrophage Activation in Pancreatic Cancer

Cullis

Siolas

Avanzi

et al. 2017

Cancer Immunology Research

134

104

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Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma (PDAC) tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis. The macropinocytic uptake of nab-paclitaxel induced macrophage immunostimulatory (M1) cytokine expression and synergized with IFNγ to promote inducible nitric oxide synthase (iNOS) expression in a TLR4-dependent manner. Nab-paclitaxel was internalized by tumor-associated macrophages in vivo, and therapeutic doses of nab-paclitaxel alone, and in combination with gemcitabine, increased the MHCII+CD80+CD86+ M1 macrophage population. These data revealed an unanticipated role for nab-paclitaxel in macrophage activation and rationalize its potential use to target immune evasion in pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Macropinocytosis of Nab-paclitaxel Drives Macrophage Activation in Pancreatic Cancer

Cullis

Siolas

Avanzi

et al. 2017

Cancer Immunology Research

134

104

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“…Further, nicotine, a nicotinic acetylcholine receptor (nAChRs) agonist, produces neuroprotective effects in cognitive disorders such as dementia and depression (Picciotto, Brunzell et al 2002; Picciotto and Zoli 2002). A toll-like receptor pathway that plays a key role in innate immunity and in the production of pro-inflammatory cytokines has been shown to be modulated by nicotine through α7nAChRs (Cui, Wang et al 2012; Cui, Zhao et al 2013). …”

Section: Behavioral Alterations In the Hiv-1tg Ratmentioning

confidence: 99%

The HIV-1 transgenic rat model of neuroHIV

Vigorito

Connaghan

Chang

2015

Brain, Behavior, and Immunity

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Despite the ability of current combination anti-retroviral therapy (cART) to limit the progression of HIV-1 to AIDS, HIV-positive individuals continue to experience neuroHIV in the form of HIV-associated neurological disorders (HAND), which can range from subtle to substantial neurocognitive impairment. NeuroHIV may also influence substance use, abuse, and dependence in HIV-positive individuals. Because of the nature of the virus, variables such as mental health co-morbidities make it difficult to study the interaction between HIV and substance abuse in human populations. Several rodent models have been developed in an attempt to study the transmission and pathogenesis of the HIV-1 virus. The HIV-1 transgenic (HIV-1Tg) rat is a reliable model of neuroHIV because it mimics the condition of HIV-infected patients on cART. Research using this model supports the hypothesis that the presence of HIV-1 viral proteins in the central nervous system increases the sensitivity and susceptibility of HIV-positive individuals to substance abuse.

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“…To avoid amplifying genomic DNA, two primers of each gene were designed to span at least one intron. A custom-designed RT-PCR array was used to measure gene expression as described previously (Cui et al, 2013, Cao et al, 2011, Wei et al, 2011). Each pair of primers and their amplicon sequences were tested using the Basic Local Alignment Search Tool (BLAST; http://blast.ncbi.nlm.nih.gov/Blast.cgi) to ensure the specificity of the designed primers for the targeted genes.…”

Section: Methodsmentioning

confidence: 99%

“…The cDNA mixture was incubated at 25°C for 10 min, 42°C for 1.5 h, and 70°C for 15 min. The PCR amplification was conducted as described previously (Cui et al, 2013, Cao et al, 2011, Wei et al, 2011). Briefly, the product was amplified in a volume of 10 μl containing 5.0 μl of 2× Power SYBR Green PCR Master Mix (Applied Biosystems) and combined sense and antisense primers (2.5 μl; final concentration 20 nM) in a 384-well plate using the 7900HT Sequence Detection System (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Modulation Effect of HIV-1 Viral Proteins and Nicotine on Expression of the Immune-Related Genes in Brain of the HIV-1 Transgenic Rats

Yang

Nesil

Connaghan

et al. 2016

J Neuroimmune Pharmacol

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The human immunodeficiency virus-1 transgenic (HIV-1Tg) rat is a non-infectious rodent model for HIV-1 infection which develops altered immune-responses similar to those in persons infected with HIV-1. HIV-1Tg and F344 rats respond significantly different to morphine, ethanol, nicotine and other psychostimulants, although the molecular mechanisms underlying these differences remain largely undetermined. Here, we compared expression of 52 immune-related genes in the prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA) of HIV-1Tg and F344 rats treated with either nicotine (0.4 mg/kg nicotine, base, s.c.) or saline for 27 days, to identify differentially expressed genes in the presence of HIV-1 with and without nicotine treatment. Using quantitative RT-PCR array, we measured RNA expression levels. Results showed that RNA expression of CASP3, CCL5, CX3CL1, CX3CR1, IL1α, LRF4, LFR7, TGFβ1 and TLR4 in NAc, CCL2, CCL5, TGFβ1 and TLR4 in PFC, and CASP3, CX3CR1, IFNα1, IL1β and IL6 in VTA was significantly modulated in HIV-1Tg rats compared with F344 rats. IL1α showed a 58% (P = 0.000072) decrease and IRF6 showed a 93.7% increase (P = 0.000227) in the NAc of HIV-1Tg compared with F344 rats; results remained significant after correction for multiple testing. We also found that several genes were significantly modulated by nicotine in HIV-1Tg rats while only a small number of immune-related genes were altered by nicotine in F344 rats. These findings imply that HIV-1 viral proteins greatly impact immune function and alter responsiveness to nicotine in certain immune-related genes.

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Identification and Characterization of Poly(I:C)-induced Molecular Responses Attenuated by Nicotine in Mouse Macrophages

Cited by 37 publications

References 69 publications

Macropinocytosis of Nab-paclitaxel Drives Macrophage Activation in Pancreatic Cancer

Macropinocytosis of Nab-paclitaxel Drives Macrophage Activation in Pancreatic Cancer

The HIV-1 transgenic rat model of neuroHIV

Modulation Effect of HIV-1 Viral Proteins and Nicotine on Expression of the Immune-Related Genes in Brain of the HIV-1 Transgenic Rats

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