Gob-5 Contributes to Goblet Cell Hyperplasia and Modulates Pulmonary Tissue Inflammation

Abstract

Gob-5 is a member of the calcium-activated chloride channel family and has been associated with allergic response in mouse models of pulmonary inflammation. Gene expression of Gob-5 has been shown to be induced in allergic airways and has been strongly associated with mucin gene regulation and goblet cell hyperplasia. We investigated the physiologic role of Gob-5 in murine models of pulmonary inflammation using mice deficient in Gob-5. After sensitization and aerosol challenge with ovalbumin (OVA), Gob-5 knockout mice exhibit significantly increased bronchoalveolar lavage (BAL) inflammation as compared with wild-type controls. The augmented inflammation in BAL consisted predominantly of neutrophils. Examination of perivascular inflammation revealed that tissue inflammation was decreased in OVA-challenged Gob-5-/- mice. OVA-challenged Gob-5 knockout mice also had decreased goblet cell hyperplasia as well as decreased mucus production. These mice also had decreased airway hypersensitivity after cholinergic provocation with methacholine. Gob-5 knockout mice were also challenged via intranasal LPS, a TLR-4 agonist. Gob-5-/- mice responded with increased neutrophilic BAL inflammation and decreased perivascular tissue inflammation as compared with wild-type controls. There was little effect on goblet cell hyperplasia and mucus production after LPS challenge. These observations reinforce findings that associate Gob-5 with goblet cell hyperplasia and mucus production in the allergic immune response, but also implicate Gob-5 in the regulation of tissue inflammation in the innate immune response.

Modulation of NF-κB and Hypoxia-Inducible Factor−1 byS-Nitrosoglutathione Does Not Alter Allergic Airway Inflammation in Mice

“…Another major feature of allergic airway inflammation is the induction of mucus metaplasia (27), and our present studies confirm that OVA sensitization and challenge resulted in enhanced mucus metaplasia, as evaluated by PAS stain ( Figure 4) and expression of IL-13, MUC5ac, and GOB5 (Table 1). GSNO administration did not affect mucus metaplasia in Alum/ OVA mice, but tended to enhance PAS staining in OVA/OVA mice, although this did not reach statistical significance ( Figure 4B; P 5 0.18).…”

Ablation of Arg1 in hematopoietic cells improves respiratory function of lung parenchyma, but not that of larger airways or inflammation in asthmatic mice

“…In agreement, the mRNA abundance of Clca3 (Gob5), which regulates mucus production, and the mucin Muc5ac were lower in OVA/OVAtreated Arg1-KO Tie2 than Arg1-Con mice. Overexpression of Clca3 exacerbates AHR in OVA/OVA-treated mice, whereas downregulation attenuates peak airway pressure (resistance) after methacholine (29,38), strongly suggesting a role for this gene in the development of peripheral responsiveness. On the basis of our observations in sections stained for the presence of collagen and reticular fibers, the improved peripheral lung function could not be caused by less remodeling in OVA/OVA-treated Arg1-KO Tie2 mice compared with Arg1-Con mice.…”

Electronegative LDL and Lipid Abnormalities in Patients Undergoing Hemodialysis and Peritoneal Dialysis

“…Its evaluation in blood plasma could represent a useful tool to follow the progression of atherosclerosis [12, 13]. In fact, some studies documented an increased proportion of LDL(–) in patients at high cardiovascular risk [12] and in familial hypercholesterolemia [14, 15], hypertriglyceridemia [16,17,18,19], type 1 and 2 diabetes mellitus [20,21,22,23,24,25,26] and athletes with intense aerobic activity [27]. In end-stage renal disease patients, Ziouzenkova et al [10] reported the presence of LDL(–) in hemodialysis (HD) patients.…”