Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses

Rubenstein, David A.; Hom, Sarah; Ghebrehiwet, Berhane

doi:10.1016/j.molimm.2015.05.020

Cited by 53 publications

(56 citation statements)

References 58 publications

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“…Others followed these studies and demonstrated synthesis of functional C1 by human colon as well as the ileum (Colten et al, 1968a, 1968b, Colten, 1971). Since these early reports, the collective work of many investigators over the years has firmly established that, fully assembled (C1) or individual components (C1r, C1s,) together with C1-INH are synthesized not only by the cells of the myeloid lineage described above, but also by a wide range of cell types that include: epithelial cells (Colten, 1976), fibroblasts (Reid and Solomon, 1977), mesenchymal cells (Morris et al, 1978), glial cells (Shäffer et al, 2000; Lynch et al, 2004; Farber et al, 2009), trophoblasts (Bulla et al, 2008; Agostonis et al, 2010), osteoclasts (Teo et al, 2012), Kupffer cells (Rubenstein et al, 2015), and more recently by mast cells (van Schaarebburg et al, 2016), The presently accepted postulate is therefore, that locally secreted C1q is an immunomodulatory molecule, which controls cellular responses by an autocrine and/or paracrine induced signaling mechanism (Castellano et al, 2004), and this paradigm is likely to be true for all the individual complement proteins secreted in situ.…”

Section: Locally Synthesized C1q Induces In Situ Functions Throughmentioning

confidence: 99%

C1q as an autocrine and paracrine regulator of cellular functions

Ghebrehiwet

Hosszu

Peerschke

2017

Molecular Immunology

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Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also synthesized extrahepatically by activated as well as non-activated cells. The question that is finally being addressed by various investigators is: are the locally synthesized proteins solely responsible for the myriad of biological functions in situ without the contribution of systemic complement? The answer is probably “yes”. Among the proteins that are synthesized locally, C1q takes center stage for several reasons. First, it is synthesized predominantly by potent antigen presenting cells such as monocytes, macrophages and dendritic cells (DCs), which by itself is a clue that it plays an important role in antigen presentation and/or DC maturation. Second, it is transiently anchored on the cell surface via a transmembrane domain located in its A chain before it is cleaved off and released into the pericellular milieu. The membrane-associated C1q in turn, is able to sense danger patterns via its versatile antigen-capturing globular head domains. More importantly, locally synthesized C1q has been shown to induce a plethora of biological functions through the induction of immunomodulatory molecules by an autocrine- or paracrine-mediated signaling in a manner that mimics those of TNFα. These include recognition of pathogen- and danger-associated molecular patterns, phagocytosis, angiogenesis, apoptosis and induction of cytokines or chemokines that are important in modulating the inflammatory response. The functional convergence between C1q and TNFα in turn is attributed to their shared genetic ancestry. In this paper, we will infer to the aforementioned “local-synthesis-for-local function” paradigm using as an example, the role played by locally synthesized C1q in autoimmunity in general and in systemic lupus erythematosus in particular.

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Section: Locally Synthesized C1q Induces In Situ Functions Throughmentioning

confidence: 99%

C1q as an autocrine and paracrine regulator of cellular functions

Ghebrehiwet

Hosszu

Peerschke

2017

Molecular Immunology

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“…It is also cytotoxic, induces apoptosis in fibroblats 8 , initiate inflammation at Kupffer 9 and enthothelial 10 cells, and alters vascular smooth muscle cells 11 . There is also an increasing number of studies in animal models implicating possible health effects.…”

Section: Introductionmentioning

confidence: 99%

Acute effects of short term use of e-cigarettes on airways physiology and respiratory symptoms in smokers with and without airways obstructive diseases and in healthy non smokers

Palamidas¹,

Tsikrika²,

Κatsaounou³

et al. 2017

Tob. Prev. Cessation

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BACKGROUND Although the use of e-cigarettes is increasing worldwide, their short and long-term effects remain undefined. We aimed to study the acute effect of short-term use of e-cigarettes containing nicotine on lung function and respiratory symptoms in smokers with airways obstructive disease (COPD, asthma), "healthy" smokers, and healthy never smokers. METHODS Respiratory symptoms, vital signs, exhaled NO, airway temperature, airway resistance (Raw), specific airway conductance (sGaw) and single nitrogen breath test were assessed before and immediately after short term use of an e-cigarette containing 11mg of nicotine among adults with COPD, asthma, ''healthy" smokers, and never-smokers. The effect of the use of nicotine-free e-cigarettes among ''healthy" never smokers was also studied. RESULTS The majority of participants reported acute cough. Short term use of nicotine e-cigarettes was associated: a) with increased heart rate in all subjects except in the COPD group, b) decreased oxygen saturation in "healthy" and COPD smokers, c) increased Raw in asthmatic smokers, "healthy" smokers, and healthy never smokers, d) decreased sGaw in healthy subjects, and e) changed slope of phase III curve in asthmatic smokers. Short-term use of nicotine-free e-cigarettes increased Raw and decreased sGaw among healthy never smokers. CONCLUSIONS Short-term use of an e-cigarette has acute effects on airways physiology and respiratory symptoms in COPD smokers, asthmatic smokers, "healthy" smokers and healthy never smokers. E-cigarette use was associated with effects in ''healthy" never smokers irrespectively of nicotine concentration. More studies are needed to investigate both short and long-term effects of e-cigarette use

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“…The toxicity of e-cig emission is poorly understood, although evidence continues to grow. Both refill e-liquids and aerosol emission from e-cigs were found to cause cellular responses in i n vitro toxicity studies pointing to potential mechanistic disease pathways (Behar et al 2014; Rubenstein et al 2015). Moreover, in vivo studies found that e-cig emission inhalation can cause deleterious effects to the lung and beyond (C.A.…”

Section: Introductionmentioning

confidence: 99%

“…It is worth noting that such toxicological studies utilized e-cig liquid instillation, which cannot reflect real e-cig exposure because chemical transformation can happen during e-liquid vaporization (Lim & Kim 2014). Another major limitation of the current toxicological studies is the lack of dosimetry consideration, and the inability to link real-world PM exposures with toxicity (Cohen et al 2015; DeLoid et al 2015; Pal et al 2015; Rubenstein et al 2015; Cohen et al 2014; Deloid et al 2014; Cohen et al 2013). Therefore, there is an urgent need to develop an integrated exposure generation platform that enables the systematic investigation of the emission profile and its physico-chemical properties, that can be used in both in-vitro and in-vivo toxicity assessment studies.…”

Section: Introductionmentioning

confidence: 99%

Development and characterization of electronic-cigarette exposure generation system (Ecig-EGS) for the physico-chemical and toxicological assessment of electronic cigarette emissions

Zhao¹,

Pyrgiotakis²,

Demokritou³

2016

Inhalation Toxicology

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Electronic cigarettes (e-cig) have been introduced as a nicotine replacement therapy and have gained increasing attention and popularity. However, while findings on possible toxicological implications continue to grow, major knowledge gaps on both the complex chemistry of the exposure and toxicity exist, prohibiting public health assessors from assessing risks. Here a versatile electronic cigarette exposure generation system (Ecig-EGS) has been developed and characterized. Ecig-EGS allows generation of real world e-cig emission profiles under controlled operational conditions, real time monitoring and time-integrated particle/gas sampling for physico-chemical characterization, and toxicological assessment (both in vitro and in vivo). The platform is highly versatile and can be used with all e-cig types. It enables generation of precisely controlled e-cig exposure while critical operational parameters and environmental mixing conditions can be adjusted in a systematic manner to assess their impact on complex chemistry and toxicity of emissions. Results proved the versatility and reproducibility of Ecig-EGS. E-cig emission was found to contain 106 – 107 particles/cm3 with the mode diameter around 200nm, under air change rate of 60/h. Elevated CO2 and volatile organic specie generation was also observed. Furthermore, environmental mixing conditions also influenced e-cig emission profile. The versatility of Ecig-EGS will enable linking of operational and environmental parameters with exposure chemistry and toxicology and help in assessing health risks.

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Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses

Cited by 53 publications

References 58 publications

C1q as an autocrine and paracrine regulator of cellular functions

C1q as an autocrine and paracrine regulator of cellular functions

Acute effects of short term use of e-cigarettes on airways physiology and respiratory symptoms in smokers with and without airways obstructive diseases and in healthy non smokers

Development and characterization of electronic-cigarette exposure generation system (Ecig-EGS) for the physico-chemical and toxicological assessment of electronic cigarette emissions

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