| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Back, M, et al.
(författare)
-
Leukotriene B4 is an indirectly acting vasoconstrictor in guinea pig aorta via an inducible type of BLT receptor
- 2004
-
Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 287:1, s. H419-H424
-
Tidskriftsartikel (refereegranskat)abstract
- Leukotriene B4(LTB4) is a potent leukocyte chemoattractant recently implicated in the pathogenesis of atherosclerosis. The aim of this study was to assess the effects of LTB4on isolated aortic preparations. Rings of guinea pig aorta were challenged with LTB4for recording mechanical responses and measurements of mediator release, and LTB4receptor (BLT1) expression was assessed by RT-PCR. Single concentrations of LTB4induced concentration-dependent contractions that were inhibited by treatment with antihistamines, indomethacin, or the thromboxane receptor antagonist BAYu3405 as well as by denudation of endothelium. In addition, LTB4increased the release of histamine and thromboxane in the bath. The contractions induced by LTB4were inhibited by either the unselective BLT receptor antagonist ONO-4057 or the selective BLT1receptor antagonist U-75302. Pretreatment with all -trans-retinoic acid enhanced the contractions and the release of histamine induced by LTB4, without affecting either the contractions induced by histamine or the histamine release evoked by calcium ionophore A23187. Analysis by RT-PCR indicated the expression of a BLT1receptor in the guinea pig aorta and that BLT1receptor mRNA was upregulated after treatment with retinoic acid. These results suggest that LTB4contracts the guinea pig aorta via an indirect mechanism involving the release of histamine and thromboxane and that this BLT1receptor-mediated response can be upregulated by all -trans-retinoic acid.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Checa, A, et al.
(författare)
-
Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment
- 2015
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 12017-
-
Tidskriftsartikel (refereegranskat)abstract
- Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P < 0.001; n = 32), but not in mild (n = 32), psoriasis relative to healthy controls (n = 32). These alterations were not reversed in severe patients (n = 16) after anti-TNF-α treatment despite significant improvement in psoriasis lesions. Circulating levels of sphingomyelins and ceramides shifted in a fatty acid chain length-dependent manner. These alterations were also observed in psoriasis skin lesions and were associated with changes in mRNA levels of ceramide synthases. The lack of S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis.
|
|
| 17. |
- Checa, A, et al.
(författare)
-
Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis
- 2015
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 21:10, s. 1271-1279
-
Tidskriftsartikel (refereegranskat)abstract
- Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS). Objectives: We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression. Methods: Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing–remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart. Results: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS ( p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND ( p<0.001), iOND ( p<0.05) and EarlyMS ( p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies ( p=0.048; p=0.027). Conclusion: HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Di Gennaro, A, et al.
(författare)
-
Targeting leukotriene B4 in inflammation
- 2014
-
Ingår i: Expert opinion on therapeutic targets. - : Informa UK Limited. - 1744-7631 .- 1472-8222. ; 18:1, s. 79-93
-
Tidskriftsartikel (refereegranskat)
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Haeggstrom, JZ, et al.
(författare)
-
Enzymes and receptors in the leukotriene cascade
- 2002
-
Ingår i: Cellular and molecular life sciences : CMLS. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 59:5, s. 742-753
-
Tidskriftsartikel (refereegranskat)
|
|
| 34. |
- Haeggstrom, JZ, et al.
(författare)
-
Leukotriene A4 hydrolase
- 2002
-
Ingår i: Prostaglandins & other lipid mediators. - : Elsevier BV. - 1098-8823. ; 68-968-69, s. 495-510
-
Tidskriftsartikel (refereegranskat)
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Haeggstrom, JZ, et al.
(författare)
-
Resolving resolvins
- 2013
-
Ingår i: Chemistry & biology. - : Elsevier BV. - 1879-1301 .- 1074-5521. ; 20:2, s. 138-140
-
Tidskriftsartikel (refereegranskat)
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Haeggstrom, JZ, et al.
(författare)
-
Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics
- 2023
-
Ingår i: Annual review of pharmacology and toxicology. - : Annual Reviews. - 1545-4304 .- 0362-1642. ; 63, s. 407-428
-
Tidskriftsartikel (refereegranskat)abstract
- Leukotrienes are potent immune-regulating lipid mediators with patho-genic roles in inflammatory and allergic diseases, particularly asthma. These autacoids also contribute to low-grade inflammation, a hallmark of cardiovascular, neurodegenerative, metabolic, and tumor diseases. Biosynthesis of leukotrienes involves release and oxidative metabolism of arachidonic acid and proceeds via a set of cytosolic and integral membrane enzymes that are typically expressed by cells of the innate immune system. In activated cells, these enzymes traffic and assemble at the endoplasmic and perinuclear membrane, together comprising a biosynthetic complex. Here we describe recent advances in our molecular understanding of the protein components of the leukotriene-synthesizing enzyme machinery and also briefly touch upon the leukotriene receptors. Moreover, we discuss emerging opportunities for pharmacological intervention and development of new therapeutics.
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
