Cigarette smoke is among the major risk factors for the development of chronic lung diseases such as COPD (chronic obstructive pulmonary disease) and emphysema [
1]. One of the key features of these diseases is the disruption of the airway wall organisation, followed by an increase in collagen deposition which leads to a progressive loss of lung function [
2]. Prolonged exposure to cigarette smoke may lead to an accumulation of macrophages and neutrophils, as observed in pulmonary emphysema, and, as shown for COPD, the inflammatory state is maintained in the disease, even if the cause has been removed (e.g. for smoke cessation after the diagnosis) [
1,
3]. One of the potential mechanisms for the perpetuation of the inflamed state may involve the control of extracellular matrix (ECM) turnover [
4]. ECM is now recognized as an instructive environment for resident and migratory cell types, and not only as a mere molecular scaffold for tissue organisation [
5,
6]. Since activation of inflammatory cells by cigarette smoke results also in the production of large amount of proteinases, as well as the decrease of inhibitors levels, the global effect is the imbalance of tissue homeostasis [
7,
8]. Moreover, the generation of proteolytic fragments (matrikins) of ECM molecules by the proteolytic enzymes secreted by different cell types, may contribute to prolong the effects of inflammation even after the cessation of the causative stimulus. This process may take place by the recruiting activity of ECM fragments towards neutrophils and monocytes, but also by the activation of growth/survival factors triggering inflammation [
9‐
11]. Matrix degrading proteinases belong to different classes, grouped on the basis of their catalytic features. In particular, matrix metalloproteinases (MMPs) constitute a broad family of more than 20 members, which share a significant structural homology and domain organisation and feature a zinc ion binding site into their catalytic domain [
12,
13]. Different subgroups of MMPs have been characterised, on the basis of their substrate specificity (e.g. collagenases, elastases and gelatinases), even if different enzymes may also share similar substrates. This overlap of target molecules, both ECM structural proteins and regulatory ones, reflects the complex organisation of matrix microenvironmental regulation. Gelatinases, also named Type IV collagenases, are two enzymes (MMP-2 or gelatinase A and MMP-9 or gelatinase B) which play a key role in a number of physiological processes. In particular, in lung ECM biology, these molecules are involved in developmental processes, as well as in tissue repair and fibrosis [
14]. Moreover, their role has been highlighted in several pathological conditions, as asthma, COPD and lung cancer. Further emerging evidences indicate that the cross-talk between different cell types and extracellular matrix molecules should be considered a determining factor influencing the outcome of inflammatory events. Furthermore, damaging external stimuli (as airborne pollutants and smoke components inhaled with respiration) can provide a variety of signals which can induce an inflammatory response. Indeed, CSE-treated lung fibroblasts are able to secrete chemotactic molecules for both neutrophils and macrophages [
15,
16]. Moreover, fibroblasts stimulated by CSE may produce prostaglandin, thereby contributing to the creation of a proinflammatory microenvironment [
17]. Furthermore, as recently stated, gelatinases produced by structural cells (as demonstrated for mouse lung fibroblasts) may play a role in the pathogenesis of COPD, and this process seems to be regulated by CSE exposure [
18]. In the lung matrix, fibroblasts regulate the composition of the ECM scaffold, by deposing new collagen and elastin molecules, both in the physiological turnover of matrix and in the reparative processes following injuries. Instead, as occurs in smoke-driven persistent inflammation, the general mechanisms of tissue repair fail, and matrix alterations may accumulate, leading to a diseased state. In this process, the correct balance between proteinases and inhibitors is critical for tissue repair and remodelling [
19]. The use of cigarette smoke as source of damage for lung cells allows mimicking the effects that may take place in vivo as a consequence of smoking and, also in animal models, smoke exposure is currently considered the best model for COPD development [
20]. Moreover, CSE has been widely used to investigate smoke effects in both oxidative and inflammatory processes in pulmonary cells [
21]. Therefore, in the present study we aimed to determine the variations in the gelatinolytic pattern of cultured human lung fibroblasts exposed to increasing concentrations of CSE. The observed modulator effect of CSE on fibroblast-secreted gelatinases may in part explain the effects due to cigarette smoke exposure in vivo, and confirm the recent hypotheses on the central role of fibroblasts in the development of chronic lung diseases.