Dysregulated inflammatory response in pulmonary hypertension is still enigmatic: what about psoriasin?

PVRI Member Authors: Djuro Kosanovic, Michael Seimetz, Oleg Pak, Himal Luitel, Akylbek Sydykov, Norbert Weissmann, Ralph T. Schermuly


Altered regulation of the immune system and enhanced inflammation were recognized as important characteristics of the pulmonary hypertension (PH) pathology.1-5 However, many underlying molecular mechanisms responsible for such uncontrolled inflammatory response in this incurable pulmonary vascular disease remained unclear and need to be further enlighten. Psoriasin (S100A7), a molecular mediator discovered over two decades ago in the pathology of psoriasis, plays a significant role in innate immunity and antimicrobial battle, skin inflammation and tumor development and progression.6-10 Due to its potent pro-inflammatory power one can expect that psoriasin may represent a novel culprit involved in the PH pathogenesis. However, up to date nothing is known regarding its potential role in the context of pulmonary vascular disease. Therefore, we would like to mobilize the scientists interested in this topic to share their valuable views and knowledge in order to unravel whether psoriasin can represent a promising target for the future investigation.

Main Article

 Despite its beneficial role as a part of the immune system defense against microorganisms, overexpression of psoriasin was found to be responsible for increased tumor growth and metastasis via orchestration of various inflammatory and pro-proliferative pathways/ mediators and events, such as increased CCL2 (chemokine (C-C motif) ligand 2)/MCP-1 (monocyte chemotactic protein-1), MMP- 9 (matrix metalloproteinase-9) and VEGF (vascular endothelial growth factor), and promoted chemotaxis of macrophages9 . In the context of PH, it is worth to mention that CCL2/ MCP-1, MMP-9 and abnormal accumulation of macrophages are already described, suggesting the hypothetical link between psoriasin and pulmonary vascular disease (Figure 1).2, 11-13 Furthermore, it was demonstrated that psoriasin stimulated neutrophil-associated production of different cytokines and chemokines, particularly IL-6 (interleukin-6) and TNF-α (tumor necrosis factor-α).14 IL-6 and TNF-α are important culprits for the PH development, indicating another theoretical possibility how psoriasin could contribute to the pathology of the pulmonary circulation (Figure 1).15, 16 Shifting from the cancer field to the lungs and respiratory disorders, psoriasin was found to be expressed in the lung epithelial cells and macrophages.17 Interestingly, psoriasin profile did not change in the patients with chronic obstructive pulmonary disease, compared to the healthy controls.17 Surprisingly, one has also to keep in mind the existence of potentially antifibrotic effects of psoriasin.10 Finally, the literature suggested that reactive oxygen species (ROS), an important feature of the PH pathobiology, are also described as inducers of psoriasin.18-20 Even more, psoriasin itself was shown to induce ROS production in epithelial and endothelial cells, indicating the probable existence of the positive loop between ROS and psoriasin.18 In addition, it was found that psoriasin acting via receptor for advanced glycation end products (RAGE) leads to augmented proliferation of endothelial cells and further increase of ROS.18 Following this line of thinking, it is worth to mention that dysregulated endothelial cells and injured endothelium are indeed involved in the complex PH pathology, so one can hypothesize that similar effects of psoriasin may be possible in the context of the pulmonary vascular endothelium (Figure 1).18, 21



Figure 1. Hypothetical involvement of psoriasin in the pathobiology of pulmonary hypertension. ROS: reactive oxygen species; M: macrophages; N: neutrophils; RAGE: receptor for advanced glycation end products; PH: pulmonary hypertension; MMP-9: matrix metalloproteinase-9; VEGF: vascular endothelial growth factor; CCL2: chemokine (C-C motif) ligand 2; MCP-1: monocyte chemotactic protein-1.

In conclusion, we propose that psoriasin, due to its potent pro-inflammatory and pro-proliferative properties acts as a molecular conductor in orchestration of different signals and events, such as ROS, inflammatory cells accumulation, cytokines, chemokines etc. in the pathological opera of the pulmonary vascular remodeling (Figure 1).

The Question for interactive discussion:

 We would like to suggest the following question to the scientific community worldwide: Is psoriasin a potential mediator with properties to be involved in aggravation of already altered inflammation in the pathobiology of pulmonary hypertension? All experts and others interested in this field are welcome to reply and express their point of view and perspectives on this topic, in the next volume of PVRI Chronicle.



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 20. Veit F, Pak O, Egemnazarov B, Roth M, Kosanovic D, Seimetz M, Sommer N, Ghofrani HA, Seeger W, Grimminger F, Brandes RP, Schermuly RT, Weissmann N. Function of NADPH oxidase 1 in pulmonary arterial smooth muscle cells after monocrotaline-induced pulmonary vascular remodeling. Antioxidants & redox signaling 2013; 19: 2213-2231.

21. Sakao S, Tatsumi K, Voelkel NF. Endothelial cells and pulmonary arterial hypertension: apoptosis, proliferation, interaction and transdifferentiation. Respiratory research 2009; 10: 95.


Pathology and Pathophysiology
Pulmonary Hypertension

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PVRI Chronicle Vol 2: Issue 2 cover image

July 2015

PVRI Chronicle Vol 2: Issue 2

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