The term lung disease describes a broad category of disorders that impair lung function. More than 35 million Americans have a preventable chronic lung disease with high mortality rates due to limited treatment efficacy. The recent increase in patients with lung disease highlights the need to increase our understanding of mechanisms driving lung inflammation. Connexins, gap junction proteins, and more specifically connexin 43 (Cx43), are abundantly expressed in the lung and are known to play a role in lung diseases. This review focuses on the role of Cx43 in pathology associated with acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and asthma. Additionally, we discuss the role of Cx43 in preventing disease through the transfer of mitochondria between cells. We aim to highlight the need to better understand what cell types are expressing Cx43 and how this expression influences lung disease.

Cell density in tumor cell three dimensional (3D) cultures affects secretome expression of components. A microenvironment characteristic shared by high-density 3D cell culture and in vivo tumor masses is poor oxygenation, with anoxia being a natural cell state in tumor centers. Until recently, the ability to study anoxia-adapted cell physiology was not possible. Using a newly-developed methodology, anoxic HeLa cell secretome expression was measured. Anoxic HeLa cell cytokine levels after 3 days’ (hypoxia inducible factor, HIF1 positive) and 10 days’ growth (HIF1 negative; anaerobic respiration) were significantly (p < 0.01) higher than normoxic controls for: IL-8 (1.8- and 3.4-fold higher, respectively), GRO (1.3- and 1.1-fold higher, respectively), and IL-11 (1.4- and 1.1-fold higher, respectively). In contrast, G-CSF, IFNα2, and CXCL-10 levels decreased over time (day 3 vs. day 10). Thus, metabolically active HeLa cells respond to the lack of oxygen, in part, by regulating the levels of cytokines produced. Cytokines expressed at increased levels, in the absence of oxygen, correspond to a secretomic profile reported for paracrine signaling pathways associated with metastasis. Further studies defining physiologic changes that occur upon anoxic growth may lead to the discovery of novel chemotherapeutic drug targets.

Glucocorticoid-resistant asthma, which predominates with neutrophils instead of eosinophils, is an increasing health concern. One potential source for the induction of neutrophil-predominant asthma is aerosolized lipopolysaccharide (LPS). Cyanobacteria have recently caused significant tidal blooms, and aerosolized cyanobacterial LPS has been detected near the cyanobacterial overgrowth. We hypothesized that cyanobacterial LPS contributes to lung inflammation by increasing factors that promote lung inflammation and neutrophil recruitment. To test this hypothesis, c57Bl/6 mice were exposed intranasally to LPS from the cyanobacterium member, Geitlerinema sp., in vivo to assess neutrophil infiltration and the production of pro-inflammatory cytokines and chemokines from the bronchoalveolar fluid by ELISA. Additionally, we exposed the airway epithelial cell line, A549, to Geitlerinema sp. LPS in vitro to confirm that airway epithelial cells were stimulated by this LPS to increase cytokine production and the expression of the adhesion molecule, ICAM-1. Our data demonstrate that Geitlerinema sp. LPS induces lung neutrophil infiltration, the production of pro-inflammatory cytokines such as Interleukin (IL)-6, Tumor necrosis factor-alpha, and Interferongamma as well as the chemokines IL-8 and RANTES. Additionally, we demonstrate that Geitlerinema sp. LPS directly activates airway epithelial cells to produce pro-inflammatory cytokines and the adhesion molecule, Intercellular Adhesion Molecule-1 (ICAM-1), in vitro using the airway epithelial cell line, A549. Based on our findings that use Geitlerinema sp. LPS as a model system, the data indicate that cyanobacteria LPS may contribute to the development of glucocorticoid-resistant asthma seen near water sources that contain high levels of cyanobacteria.

Probiotics are an attractive target for reducing the incidence of allergic disease. Bacillus subtilis is a gut-associated probiotic bacteria that can suppress allergic lung disease; however, it is not clear for how long this protection lasts. We exposed C57Bl/6 mice to B. subtilis via oral gavage and challenged them with intranasal house-dust mite for up to 8 weeks. We found that B. subtilis treatment was able to provide protection from eosinophil infiltration of the airways for 3 weeks. This loss of protection correlated with an increase in the eosinophil chemoattractant CCL24. Additionally, we demonstrate that B. subtilis treatment altered the bacterial composition by increasing the phylum Bacteroidetes and Verrucomicorbiota. The phylum Verrucomicorbiota was reduced in B. subtilis-treated mice at 8 weeks when protection was lost. These results support B. subtilis as a prophylactic for preventing the production of allergic lung disease and highlights that protection can last up to 3 weeks. This work also expands our understanding of how B. subtilis mediates protection and that in addition to modifying the immune system it is also altering the host microbiota.

Silver Sulfadiazine (SVD), Collagenase (Col) and Bacitracin (Bac) are common topical agents used in the management of burn and wound patients. Frequently, these agents are combined in order to synergize the effect. This study was intended to evaluate the antimicrobial activity of these commonly used agents when used individually and together. The antimicrobial activity of Silver Sulfadiazine (SVD), Collagenase (Col) and Bacitracin (Bac) were applied to different bacterial growth plates and a control plate. Zones of inhibition (ZOI) were evaluated and measured. Any changes in the zone of inhibition by 3 millimeters or more was considered to be significant. Collagenase was effective against Pseudomonas (ZOI 4 mm) while not effective against Staphylococcus aureus, E Coli or Streptococcus. Silver Sulfadiazine is effective against both Pseudomonas and Staphylococcus Aureus (ZOI 4 mm for both). Combining both agents decreased the efficacy of Silver Sulfadiazine against Staphylococcus (ZOI 2 mm). The effect against pseudomonas, however, was unaffected by the combination. Silver Sulfadiazine is effective against E.Coli (ZOI 3 mm) and Sreptococcus Pyogens (8 mm). Collagenase was not effective against either. However when Collagenase was combined with Silver Sulfadiazine, it decreased the SVD effect against Strep Pyogens significantly (ZOI 4 mm). Bacitracin was effective against Streptococcus and Staphylococcus (ZOI 9 mm and 7 mm respectively), combining Bacitracin with Collagenase decreased its effect on Streptococcus and Staphylococcus significantly (ZOI 4 mm and 3 mm respectively). Silver Sulfadiazine is used commonly in the management of wounds to prevent and treat infections, Collagenase is often combined with Silver Sulfadiazine for its proteolytic activity. While Collagenase alone appears to have antimicrobial activity against Pseudomonas it does reduce the efficacy of Silver Sulfadiazine against Staphylococcus, Streptococcus and E. Coli. Collagenase also reduces the effect of Bacitracin against Streptococcus and Staphylococcus. Although collagenase has strong proteolytic effects and is useful in debridement, it reduces the antimicrobial effect of SVD and Bacitracin when used in combination.