Abstract
Recent experiments have shown that in patients with psoriasis, highly elevated levels of nitric oxide (NO) are released at the surface of psoriatic plaques. Nitric oxide is a central biological regulator of many aspects of physiology, and it is a natural possibility that the high nitric oxide levels in psoriasis play a causal role in the onset of the disease. Here, we use mathematical modelling to investigate this possibility. We begin by discussing a simple model consisting of a single equation for nitric oxide concentration, which enables nitric oxide secretion rates in the basal epidermis to be calculated from the observed NO release rates at the skin surface. Using this key parameter value, we then develop an extended model that tests the hypothesis that nitric oxide regulates the formation of the extended rete pegs seen in psoriatic plaques. This occurs via the peroxynitrite-dependent activation of the collagenase MMP-8, which is produced by neutrophils present at high levels in psoriatic plaques. The plausibility of the hypothesis is demonstrated and specific testable quantitative predictions about the roles of the various cell types and signalling molecules are made. © 2002 Academic Press.
| Original language | English |
|---|---|
| Pages (from-to) | 1-16 |
| Number of pages | 16 |
| Journal | Journal of Theoretical Biology |
| Volume | 214 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2002 |
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Mathematical modelling of nitric oxide regulation of rete peg formation in psoriasis. / Savill, Nicholas J.; Weller, Richard; Sherratt, Jonathan A.
In: Journal of Theoretical Biology, Vol. 214, No. 1, 2002, p. 1-16.Research output: Contribution to journal › Article
TY - JOUR
T1 - Mathematical modelling of nitric oxide regulation of rete peg formation in psoriasis
AU - Savill, Nicholas J.
AU - Weller, Richard
AU - Sherratt, Jonathan A.
PY - 2002
Y1 - 2002
N2 - Recent experiments have shown that in patients with psoriasis, highly elevated levels of nitric oxide (NO) are released at the surface of psoriatic plaques. Nitric oxide is a central biological regulator of many aspects of physiology, and it is a natural possibility that the high nitric oxide levels in psoriasis play a causal role in the onset of the disease. Here, we use mathematical modelling to investigate this possibility. We begin by discussing a simple model consisting of a single equation for nitric oxide concentration, which enables nitric oxide secretion rates in the basal epidermis to be calculated from the observed NO release rates at the skin surface. Using this key parameter value, we then develop an extended model that tests the hypothesis that nitric oxide regulates the formation of the extended rete pegs seen in psoriatic plaques. This occurs via the peroxynitrite-dependent activation of the collagenase MMP-8, which is produced by neutrophils present at high levels in psoriatic plaques. The plausibility of the hypothesis is demonstrated and specific testable quantitative predictions about the roles of the various cell types and signalling molecules are made. © 2002 Academic Press.
AB - Recent experiments have shown that in patients with psoriasis, highly elevated levels of nitric oxide (NO) are released at the surface of psoriatic plaques. Nitric oxide is a central biological regulator of many aspects of physiology, and it is a natural possibility that the high nitric oxide levels in psoriasis play a causal role in the onset of the disease. Here, we use mathematical modelling to investigate this possibility. We begin by discussing a simple model consisting of a single equation for nitric oxide concentration, which enables nitric oxide secretion rates in the basal epidermis to be calculated from the observed NO release rates at the skin surface. Using this key parameter value, we then develop an extended model that tests the hypothesis that nitric oxide regulates the formation of the extended rete pegs seen in psoriatic plaques. This occurs via the peroxynitrite-dependent activation of the collagenase MMP-8, which is produced by neutrophils present at high levels in psoriatic plaques. The plausibility of the hypothesis is demonstrated and specific testable quantitative predictions about the roles of the various cell types and signalling molecules are made. © 2002 Academic Press.
UR - http://www.scopus.com/inward/record.url?scp=0036352521&partnerID=8YFLogxK
U2 - 10.1006/jtbi.2001.2400
DO - 10.1006/jtbi.2001.2400
M3 - Article
VL - 214
SP - 1
EP - 16
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
SN - 0022-5193
IS - 1
ER -