Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis

Analysis of Boswellic Acid Contents and Related Pharmacological Activities of Frankincense-Based Remedies That Modulate Inflammation

“…Recently, we showed that AKBA binds an allosteric site in 5-LOX thereby shifting the regiospecificity towards a 12-lipoxygenating enzyme, which in neutrophils led to decreased LT and 5-HETE levels but increased the amounts of 12/15-LOX products and elevated anti-inflammatory specialized pro-resolving mediators (SPM) in 5-LOX-transfected HEK cells [ 18 ]. Such a pattern was also revealed in the present study for “Sallaki ® Tablets” and “BOSWELLIASAN ® ” that inhibited the formation of LTs and 5-HETE in human primary neutrophils that had been challenged by physiological relevant bacterial exotoxins [ 16 ] and at the same time, shifted AA conversion towards 12-HETE, as observed for AKBA [ 18 ]. BAs were shown to inhibit constitutively activated NF-kappaB signaling by blocking IkappaB kinase activity [ 33 ], which might underly the suppressive effects on pro-inflammatory cytokine release [ 19 ].…”

“…Next, we assessed how the frankincense-based preparations affect 5-LOX activity in intact human neutrophils that are major producers of leukotrienes [ 15 ], challenged with Staphylococcus aureus -conditioned medium (SACM) containing exotoxins for eliciting 5-LOX product formation [ 16 ]. Freshly isolated neutrophils from human blood were pre-incubated with the frankincense-based remedies for 15 min prior to addition of 1% SACM for 90 min at 37 °C.…”

“…Freshly isolated neutrophils from human blood were pre-incubated with the frankincense-based remedies for 15 min prior to addition of 1% SACM for 90 min at 37 °C. Formed 5-LOX products (LTB 4 and its trans-isomer and 5-HETE) were assessed by UPLC-MS-MS as reported [ 16 ]. In agreement with the results using isolated 5-LOX, “Sallaki ® Tablets” and “BOSWELLIASAN ® ” caused potent suppression of 5-LOX product formation with IC 50 of 15 and 7.5 µg/mL, respectively, while “H15 Ayurmedica ® ” was less efficient (IC 50 = 39 µg/mL) ( Figure 4 a).…”

“…Next, we assessed how the frankincense-based preparations affect 5-LOX activity in intact human neutrophils that are major producers of leukotrienes [15], challenged with Staphylococcus aureus-conditioned medium (SACM) containing exotoxins for eliciting 5-LOX product formation [16]. Freshly isolated neutrophils from human blood were pre-incubated with the frankincense-based remedies for 15 min prior to addition of 1% SACM for 90 min at 37 • C. Formed 5-LOX products (LTB 4 and its trans-isomer and 5-HETE) were assessed by UPLC-MS-MS as reported [16]. In agreement with the results using isolated 5-LOX, "Sallaki ® Tablets" and "BOSWELLIASAN ® " caused potent suppression of 5-LOX product formation with IC 50 of 15 and 7.5 µg/mL, respectively, while "H15 Ayurmedica ® " was less efficient (IC 50 = 39 µg/mL) (Figure 4a).…”

Phenol-soluble modulins α are major virulence factors of Staphylococcus aureus secretome promoting inflammatory response in human epidermis

“…In neutrophils, PSMs exert pro-inflammatory action through the FPR2 receptor. It has been shown that blocking FPR2 with its antagonist WRW4 resulted in a complete inhibition of neutrophil response to PSMs, whereas blocking FPR1 and FPR3 had no effect [ 21 , 32 , 50 ]. In addition, WRW4 was able to inhibit the mast cell degranulation induced by δ-toxin in a mouse model [ 51 ].…”