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Table 2 Literature overview on selected proteins differentially abundant in current smokers as compared to never smokers

From: Smoking induces sex-specific changes in the small airway proteome

Protein name

Entrez symbol

(Uniprot ID)

Abundance in current smokers

Relevant literature findings, summary and reference

Advanced glycosylation end product-specific receptor, soluble

Decoy receptor for RAGE (a pattern recognition receptor of the immunoglobulin super-family) [45, 67]

RAGE signalling is a key driver of inflammation, oxidative stress and alveolar tissues damage in many pulmonary diseases, including COPD and is inhibited by sRAGE [45, 67]

 sRAGE

Circulating sRAGE is decreased in COPD [45]

 (Q15109)

Decrease in serum sRAGE is reported to occur already within 1 h after smoking, reaches its maximum after 8 h and is not fully restored even after 48 h [45]

Testican-2

Forming part of the extracellular matrix

 SPOCK2

It has been suggested to contribute to lung barrier function providing protection against influenza virus infection by restricting entry of the virus into epithelial cells [68]

 (Q92563)

 

It is known to modulate matrix metalloproteinases expression and activation [48]

Follistatin-related protein 3

A secreted glycoprotein structurally and functionally related to follistatin [69]

 FSTL3

It binds and antagonises actions of members of the transforming growth factor beta (TGFβ) superfamily such as activin A (an important regulator of cigarette smoke-induced inflammation) [47, 69]

 (O95633)

Follistatin, an activin A inhibitor, has been seen to be decreased in cigarette smoke-exposed human bronchial epithelial cells and administration of follistatin was found to attenuate cigarette smoke-induced airway inflammation in mice [47]

Protein S

Involved in the inhibition of coagulation, clearance of apoptotic cells and inhibition of inflammation [70]

 PROS1

In plasma, 30–40% of protein S exists in its free form and the remainder is forming a complex with C4b-binding protein (C4BP), an important regulator of complement activation by the classical pathway [70]

 (P07225)

Protein S localizes C4BP to apoptotic cells where C4BP can down-regulate complement activation and therefore inhibit inflammation at the surface of apoptotic cells [70]

 

Binding of free protein S to the surface of apoptotic cells also enhances phagocytosis of apoptotic cells by macrophages [71]

Adiponectin

Anti-inflammatory adipokine that inhibits proinflammatory cytokines and induces anti-inflammatory cytokines [72]

 ADIPOQ

Studies have shown that subjects with emphysema have increased levels of adiponectin in BAL fluid while current smokers without COPD have reduced levels of adiponectin in BAL fluid [72]

 (Q15848)

 

Beta-2-microglobulin

Component of the class I major histocompatibility complex (MHC I)

 B2M

 

Identified as a proaging factor [73]

 (P61769)

 

Studies have shown that serum β2M is significantly elevated in patients with COPD and the expression of β2M is significantly higher in lung tissue of emphysema [73]

Heat shock protein 90

Functions as a molecular chaperone and contributes to the folding, maintenance of structural integrity and proper regulation of a subset of cytosolic proteins [74]

 HSP90

Plays an important role in the UPR ("unfolded protein response") [58]

 (P07900)

The expression of heat shock proteins is increased in the alveolar epithelial cells exposed to cigarette smoke extract [62]

 (P08238)

 

Translationally-controlled tumor protein (Fortilin)

A pro-survival molecule [61]

 TCTP

Plays an important role in the UPR where it protects cells from the apoptotic cell death [61]

 (P13693)

 

Ferritin

An iron-storage protein [6]

 (P02794)

Increased levels could indicate iron overload [6]

 (P02792)

Increased in serum and BAL fluid in current smokers [6, 75]

Macrophage mannose receptor 1

A pattern recognition receptor found on M2 macrophages which are considered to have anti-inflammatory, wound-healing properties and are involved in the removal of apoptotic cells [76]

 MRC1, CD206

Reduced expression of MRC1 has been associated with a reduced removal of apoptotic cells in COPD [63]

 (P22897)

Lack of MRC1 may also result in upregulation of pro-inflammatory cytokines during endotoxin induced lung inflammation in mice [77]

Interleukin-1 receptor-like 1

A receptor for interleukin-33 (IL-33) [64, 65]

 IL1RL1, ST2

Exists in several isoforms [64, 65]

 (Q01638)

The membrane-bound ST2 binds IL-33, inducing pro-inflammatory immune responses and cytokine production and subsequently eliciting airway inflammation [64, 65]

 

The soluble form of ST2 functions as a decoy receptor neutralizing IL-33 activity and is therefore considered to have an anti-inflammatory function [64, 65]

Adenylate kinase isoenzyme 1

Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism

 AK1

 

 (P00568)