| 421. |
|
|
| 422. |
|
|
| 423. |
- Tengroth, L, et al.
(författare)
-
Activation of Activin receptor-like kinases curbs mucosal inflammation and proliferation in chronic rhinosinusitis with nasal polyps
- 2018
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 1561-
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic rhinosinusitis with nasal polyps (CRSwNP) is a widespread disease causing obstruction of the nasal cavity. Its cause remains unclear. The transforming growth-factor beta (TGF-β) superfamily and their receptors, termed Activin receptor-like kinases (ALKs), have recently been suggested to play a role in local airway inflammation, but have so far not been evaluated in human nasal epithelial cells (HNECs) from CRSwNP patients. We demonstrated that ALK1–7 were expressed in the nasal polyp epithelium, and the expression of ALK1-6 was markedly elevated in polyps compared to nasal mucosa from healthy controls. Stimulation with the ALK ligand TGF-β1 decreased Ki67 expression in HNECs from CRSwNP patients, not evident in controls. Likewise, TGF-β1, Activin A and Activin B, all ALK ligands, decreased IL-8 release and Activin A and Activin B reduced ICAM1 expression on HNECs from CRSwNP patients, not seen in controls. Pre-stimulation with TGF-β1, Activin A, BMP4 and Activin B attenuated a TNF-α-induced ICAM1 upregulation on HNECs of CRSwNP. No effect was evident in controls. In conclusion, an increased expression of ALK1-6 was found on polyp epithelial cells and ligand stimulation appeared to reduce proliferation and local inflammation in polyps.
|
|
| 424. |
|
|
| 425. |
|
|
| 426. |
|
|
| 427. |
|
|
| 428. |
- Turubanova, VD, et al.
(författare)
-
Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 7205-
-
Tidskriftsartikel (refereegranskat)abstract
- The immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm2 (λex 615–635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.
|
|
| 429. |
- Van Crombruggen, K, et al.
(författare)
-
Innate lymphoid cells in the upper airways: importance of CD117 and IL-1RI expression
- 2018
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52:6
-
Tidskriftsartikel (refereegranskat)abstract
- Although type 1, 2 and 3 innate lymphoid cells (ILC1s, ILC2s and ILC3s, respectively) are emerging as important cell populations regulating tissue homeostasis, remodelling and inflammation, a vast majority of our knowledge stems from in vitro and murine experiments, and requires thorough confirmation in human diseases.Relative levels of ILCs were evaluated by means of flow cytometry in freshly resected human upper airways mucosa of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP), taking into account the patient's clinical parameters and disease comorbidities.We report that the CD117 and interleukin-receptor type I (IL-1RI) expression status of human ILC2s depends on the local tissue environment. Only CD117+ IL-1RI+ ILC2s, exclusively present in CRSwNP, possess an interrelationship with type 2 T-helper cell cytokine and eosinophil levels in human upper airway mucosa. In CRSsNP, mainly CD117−IL-1RI− ILC2s are increased, yielding lower eosinophilia in this disease despite the high levels of ILC2s.These data unveil that the CD117− and CD117+ fractions within the native human ILC2 population are not a random phenomenon, in contrast to what could be concluded from in vitro data, and that the IL-1RI expression is not ubiquitous in ILC2s in vivo in humans, which cannot be assessed via in vitro and murine experiments.
|
|
| 430. |
|
|
