Inflammation of the respiratory tract is associated with CCL28 and CCR10 expression in a murine model of allergic asthma

Abstract

Mouse models and in vitro cell culture were used to examine airway expression of the mucosal chemokine CCL28. Low levels of constitutively expressed mRNA were observed in transformed murine epithelial cells, but high levels could be induced by stimulation. Cytokines that signal through NF-B, including IL-1␤ and TNF-␣ or via JAK-STAT pathway including oncostatin M induced CCL28 in airway epithelial cells in vitro. Immunohistochemistry of murine airway tissue revealed that constitutive expression of CCL28 protein in vivo was low and not ubiquitous. However, abundant expression was detected in epithelia and lymphoid aggregates following allergic sensitization and challenge with ovalbumin. This was accompanied by increased detection of cells expressing CCR10 protein and mRNA in inflamed airways. Taken together, these data support a role for CCL28 in contributing to allergen driven airway pathologies, show that proinflammatory cytokines can induce this signal and suggest a role for CCR10 expressing cells in airway inflammation.

IL-17A Induces CCL28, Supporting the Chemotaxis of IgE-Secreting B Cells

“…It is important, however, to note that these data are not informative of the specific role of these proteins in asthma, which will require larger studies with control data from healthy volunteers and parallel studies in knockout animal models. Whilst care needs to be exercised in extrapolating from small patient cohorts, these results are consistent with previous mouse studies [3,7] and suggest a comparable response in humans.…”

“…CCL28 and IL-17A are elevated in the inflamed airway [3,6,7,15,28] and IL-17A is a potent inducer of chemokines [26], therefore the role of IL-17A in the regulation of CCL28 was examined. Firstly, the expressions of IL-17RA and IL-17RC, the two receptors that mediate cellular responses to IL-17A, were verified in airway cells.…”

“…CCL28 levels in murine hyper-responsive airways are increased compared to controls and correlate with the localized expression of the receptors CCR3 and CCR10; this has been attributed to the infiltration of eosinophils and T cells bearing these receptors [3,7]. An examination of sputum, from a small cohort of steroid-naive human asthmatic subjects (fig.…”

“…Six hundred microliters of recombinant protein, A549-conditioned or serum-free (control) medium were added directly into the lower chambers and 2 × 10 5 B cells added to the upper chamber. To verify the specificity of migration, B cells were incubated with 250 ng/ml anti-CCR10 [7] for 30 min prior to addition or CCL28 was neutralized by 30 µg/ml anti-human CCL28 (lower chamber; R&D Systems). Cells were allowed to migrate for 2 h at 37°C in 5% CO 2 and counted from 5 random fields of view imaged by an inverted microscope with a digital camera.…”

“…It recruits eosinophils, IgA+ antibody-secreting cells (ASC) and T cells via CCR3 and CCR10 [3,4,5]. This chemokine is elevated in human asthmatic biopsy [6] and is associated with increased allergic pathology in murine models of airway disease, with increased CCL28 expression linked to the recruitment of both CCR10- and CCR3-expressing cells [3,7]. In addition, when CCL28 antisera were administered to mice with established airway inflammation, mucus cell metaplasia, airway hyper-responsiveness and peribronchial eosinophilia were reduced [3].…”