CXC Chemokines in the Pathogenesis of Pulmonary Disease and Pharmacological Relevance

Abstract

Chemokines and their receptors play important roles in the pathophysiology of many diseases by regulating the cellular migration of major inflammatory and immune players. The CXC motif chemokine subfamily is the second largest family, and it is further subdivided into ELR motif CXC (ELR+) and non-ELR motif (ELR-) CXC chemokines, which are effective chemoattractants for neutrophils and lymphocytes/monocytes, respectively. These chemokines and their receptors are expected to have a significant impact on a wide range of lung diseases, many of which have inflammatory or immunological underpinnings. As a result, manipulations of this subfamily of chemokines and their receptors using small molecular agents and other means have been explored for potential therapeutic benefit in the setting of several lung pathologies. Furthermore, encouraging preclinical data has necessitated the progression of a few of these drugs into clinical trials in order to make the most effective use of interventions in the development of viable targeted therapeutics. The current review presents the understanding of the roles of CXC ligands (CXCLs) and their cognate receptors (CXCRs) in the pathogenesis of several lung diseases such as allergic rhinitis, COPD, lung fibrosis, lung cancer, pneumonia, and tuberculosis. The potential therapeutic benefits of pharmacological or other CXCL/CXCR axis manipulations are also discussed.

Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis

“…A previous study showed that CD69 is one of the lung-resident markers [ 39 ]. CXCL12, the ligand of CXCR4, is abundant in the lung [ 40 ] and the CXCR4/CXCL12 axis was important in lung injury/fibrosis [ 41 ]. Thus, CD69, CXCR4 and other markers expressed by Tph cells could promote the chemotaxis of Tph cells to the lung in ABPA coordinately.…”

“…The Tph cells of ABPA patients expressed chemokines for neutrophils such as CXCL2, CXCL3 and CXCL8. Studies show that they are involved in the allergic inflammation and could exaggerate type 2 response [ 41 – 43 ]. Besides, CXCL8 might increase the bronchoconstriction by stimulating airway smooth muscle cells in cystic fibrosis and asthma [ 42 ], both of which are major concomitant diseases of ABPA.…”

Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study

“…MIG and IP-10 were the most effective diagnostic markers for differentiating between asymptomatic/mildly symptomatic COVID-19 patients and COVID-19 patients with pneumonia without respiratory failure. Both chemokines belong to the CX subfamily and the non-ELR subgroup ( 36 , 37 ). Non-ELR chemokines lack the ELR (Glu-Leu-Arg) motif, and they act as chemoattractants and activators of monocytes, dendritic cells, lymphocytes (T, B, and NK cells), basophils and eosinophils, without angiogenic potential ( 38 , 39 ).…”

Long-lasting cigarette smoking alterations in immune function occur in cannabis smokers, possibly rendering them vulnerable to smoking-related tumors in later life

“…upregulation of the bacterially induced inflammatory cytokine C-X-C motif chemokine ligand 5 (CXCL5) [1,2].…”

“…Smoking has a lasting impact on the immune system, including alterations in adaptive immune response cytokine production. Specifically, active smoking is associated with an upregulation of the bacterially induced inflammatory cytokine C-X-C motif chemokine ligand 5 (CXCL5) [1, 2].…”