J.H. Sisson’s research while affiliated with University of Nebraska at Omaha and other places

... Donors: donor 1, filled circles (•); donor 2, empty squares (□); donor 3, empty circles (ο) significant subpopulation of the monolayer [39]. Previous studies have shown shortening or loss of cilia, as well as decreases in CBF, are a direct result of the volatile organic compounds [40][41][42][43][44]. Whereas CS has a high concentration of volatile organic compounds, EC aerosols have concentrations that vary with the abundance of flavoring components and the glycerol:propylene-glycol ratio in the e-liquid [45][46][47][48]. ...

Reference:

Effect of sub-chronic exposure to cigarette smoke, electronic cigarette and waterpipe on human lung epithelial barrier function

... Namely, infiltration of polymorphonuclear neutrophils into the bronchi was very severe on the day of exposure, milder on day 3 than on the day of exposure, and not observed on day 14 after exposure. SOD is a superoxide scavenger (McCord and Fridovich 1968) from epithelial cells (Linder and Sisson 1994), the rapid increase in SOD activity and neutrophils after exposure strongly suggests that superoxide was released into the alveoli mainly from neutrophils. The rapid and striking increase in cq-AT activity in BALF on the day of exposure indicates that EL and other proteases were released from the infiltrating neutrophils into the alveolar area (Janoff 1985a) because ~I-AT is reported to act as a specific protective enzyme against tissue injuries caused by EL (Janoff 1985 b). ...

Reference:

Inhalation toxicity of diborane in rats assessed by bronchoalveolar lavage examination

... In analogy to the situation in Paramecium (Hamasaki et al., 1991;Hamasaki et al., 1989), cAMP possibly regulates CBF by activating PKA localized to the axoneme by its A kinase anchoring protein (Kultgen et al., 2002). PKA in turn phosphorylates a dynein light chain (Kultgen et al., 2002;Salathe et al., 1993;Sisson et al., 2000). Even though cells apically permeabilized using saponin have not been found to change ciliary beating upon addition of cAMP (Lansley et al., 1992), isolated axonemes have been shown to beat faster when cAMP levels are increased (Wyatt et al., 2005). ...

Reference:

Real-time analysis of cAMP-mediated regulation of ciliary motility in single primary human airway epithelial cells

... Mucociliary clearance and cellular migration/wound repair are important innate immune functions of epithelial cells that protect and repair the lung from deleterious effects of inhaled pollutants, allergens, and pathogens262728. Exposure to cigarette smoke, bacterial pathogens, diesel exhaust particles, and organic dusts slow ciliary motility and decrease epithelial cell migration [14,293031. Our studies demonstrate that MyD88 KO epithelial cells have normal baseline ciliary beat function and respond normally to the immunostimulatory non-TLR agent, procaterol (Fig. 1b ). ...

Reference:

MyD88 in lung resident cells governs airway inflammatory and pulmonary function responses to organic dust treatment

... These changes in the lung alter the earliest responses to infection, which can potentially change the lung's defense against viral infection. In animal models of pulmonary viral infections, alcohol administration is associated with changes that make infection more likely (Simet et al., 2013). In addition, alcohol administration is associated with increased morbidity and mortality in the animals (Meyerholz et al., 2008) as well as higher viral titers and more severe pathology (Jerrells et al., 2007;Warren et al., 2016Warren et al., , 2019. ...

Reference:

COVID‐19 patients with documented alcohol use disorder or alcohol‐related complications are more likely to be hospitalized and have higher all‐cause mortality

... Because PKC activity is known to potentiate the proinflammatory responses in BECs exposed to HDE, MaR1's mechanism of reducing inflammatory cytokine release is likely mediated in part through these inhibitory actions on PKCα and PKCε. Previous experiments by our laboratory have shown that PKA activation negatively regulates the pro-inflammatory cytokine release in BECs induced by HDE exposure [32]. We therefore sought to determine whether or not MaR1 was inhibiting the release of pro-inflammatory cytokines not only by inhibiting PKCα and PKCε activity, but also through the activation of PKA. ...

Reference:

Maresin-1 reduces the pro-inflammatory response of bronchial epithelial cells to organic dust

... Ciliated mouse cells have also served as a system for studying the effects of several environmental factors on ciliary function. Cultured mTECs have been used to study the effects of alcohol on ciliary motility and its regulatory pathways [298][299][300], as well as the effect of hypoxic conditions on gene transcription during multiciliated cell differentiation [301]. Protective response to bacteria was assessed in mTECs incubated with E. coli prior to culturing under ALI conditions [296], and effect of mechanical pressure on ciliary stimulation was assessed by treating ALI mTECs with an air puff at the apical surface [302]. ...

Reference:

Motile cilia genetics and cell biology: big results from little mice

... These exposures elicit innate immune responses through activation of Toll-like receptors (TLR; i.e. TLR2, TLR4, TLR9), scavenger receptors, and myeloid differentiation factor 88 (MyD88) signaling pathways [6][7][8][9]. Human and animal studies have also described roles for activated lung macrophages, CD4 + T cells, and a Th1/Th17 lung microenvironment as related to agriculture organic dust exposures [10][11][12][13][14]. Earlier animal studies demonstrated that repetitive organic dust extract (ODE) exposures induce discrete peribronchiolar and lung parenchymal lymphoid aggregates comprised of both T and B cells [15]. However, the precise role of B cells in mediating agriculture organic dust-induced lung inflammation has not been thoroughly investigated. ...

Reference:

A role for B cells in organic dust induced lung inflammation

... PDE5 was first identified in the lungs by Lincoln and Corbin [16] as a cGMP-binding protein unique from PKG. Indeed, PDE5 has been identified in ciliated airway epithelium [17], along with PDE2 [18] and PDE4 [19]. These PDEs function to hydrolyze respective cyclic nucleotides, thus returning cilia beating to homeostatic baseline levels. ...

Reference:

Cyclic GMP and Cilia Motility

... The first set of experiments was designed to investigate the effect of acute ethanol exposure on liver functions and on hepatic GABA signaling. Mice in the ethanol group were administered by intraperitoneal (i.p.) injection of ethanol (3.0 g kg −1 ) (Happel et al., 2006;Oldenburg, Wyatt, Factor, & Sisson, 2009). All mice treated with ethanol received the same concentration of ethanol (20% v/v in 0.9% saline), which was reported to reduce ethanol absorption from intestine tract (Kinoshita, Ijiri, Ameno, Fuke, & Ameno, 1995). ...

Reference:

Protective roles of hepatic gamma-aminobutyric acid signaling in acute ethanol exposure-induced liver injury